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Zaffagnini M, Boffa A, Andriolo L, Raggi F, Zaffagnini S, Filardo G. Orthobiologic therapies delay the need for hip arthroplasty in patients with avascular necrosis of the femoral head: A systematic review and survival analysis. Knee Surg Sports Traumatol Arthrosc 2025; 33:1112-1127. [PMID: 39543728 PMCID: PMC11848991 DOI: 10.1002/ksa.12532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/21/2024] [Accepted: 10/23/2024] [Indexed: 11/17/2024]
Abstract
PURPOSE The aim of this systematic review and survival analysis was to quantify the benefits of orthobiologic augmentation therapies for the treatment of avascular necrosis (AVN) of the femoral head and identify the most effective approach to delay the need for total hip arthroplasty (THA). METHODS A systematic review of the literature was performed on PubMed, Scopus, and Cochrane on clinical studies on orthobiologic therapies used alone or as an augmentation to core decompression or other procedures to address hip AVN. A qualitative analysis of the different biological therapies applied was performed. Afterward, the results of these procedures were quantitatively analysed to document their survivorship from THA compared to treatment groups without orthobiologics. Kaplan-Meier analysis was performed for all studies and then by categorising orthobiologics into treatment subgroups. RESULTS A total of 106 studies were included (4505 patients). Different orthobiologic approaches have been evaluated: cell-based therapies including bone marrow aspirate concentrate (BMAC) and bone marrow mesenchymal stromal cells (BM-MSCs), platelet-rich plasma (PRP), or other bioactive molecules applied in the osteonecrotic area or as intra-arterial injections. The survival analysis at 120 months documented a higher (p < 0.0005) cumulative survivorship with orthobiologics (69.4%) compared to controls (48.5%). The superiority was shown specifically for BMAC (p < 0.0005), BM-MSCs (p < 0.0005), intra-arterial (p < 0.0005) and PRP (p = 0.011) approaches, but the direct comparison of these approaches with their controls confirmed benefits only for BMAC (p < 0.0005). CONCLUSION This systematic review and survival analysis demonstrated that orthobiologics have the potential to improve survivorship in patients affected by hip AVN. In particular, the specific analysis of different orthobiologic products supported relevant benefits for BMAC augmentation in terms of survival from the need for THA, while no clear benefits were confirmed for other orthobiologics. LEVEL OF EVIDENCE Level III.
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Affiliation(s)
- Marco Zaffagnini
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Angelo Boffa
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Luca Andriolo
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Federico Raggi
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Stefano Zaffagnini
- Clinica Ortopedica e Traumatologica 2, IRCCS Istituto Ortopedico RizzoliBolognaItaly
| | - Giuseppe Filardo
- Applied and Translational Research (ATR) Center, IRCCS Istituto Ortopedico RizzoliBolognaItaly
- Department of SurgeryEOC, Service of Orthopaedics and TraumatologyLuganoSwitzerland
- Faculty of Biomedical SciencesUniversità Della Svizzera ItalianaLuganoSwitzerland
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Xu RD, Duan SY, Liang HR, Sun M, Wen H, Zhou XT, Liu HF, Cai ZC. Efficacy study of platelet-rich plasma combined with core decompression and bone grafting in the treatment of early-stage avascular necrosis of the femoral head: a retrospective study. BMC Musculoskelet Disord 2024; 25:796. [PMID: 39385153 PMCID: PMC11462962 DOI: 10.1186/s12891-024-07920-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 10/04/2024] [Indexed: 10/11/2024] Open
Abstract
OBJECTIVE This study aimed to evaluate the effectiveness of combined core decompression (CD), bone grafting (BG), and platelet-rich plasma (PRP) in treating early-stage avascular necrosis of the femoral head (ANFH). METHODS A retrospective study was conducted on 74 patients (85 hips) with Ficat-Arlet stage I-II ANFH who were treated at our hospital between May 2015 and May 2018. The control group (20 patients, 22 hips) received symptomatic treatments, including weight-bearing reduction and oral analgesics. The CD + BG group (29 patients, 34 hips) underwent CD and β-tricalcium phosphate bone grafting. The PRP combination group (25 patients, 29 hips) received PRP injections in addition to CD and BG. Patients were followed up for five years to assess the necessity for total hip arthroplasty (THA). Data analysis was performed on those from the CD + BG and PRP groups who did not require THA. Clinical outcomes were evaluated using the Visual Analog Scale (VAS), Harris Hip Score (HHS), and the proportion of patients not accepting THA. RESULTS At the five-year follow-up, the rate of THA in the control group was 68.18% (15/22), while in the CD + BG group and the PRP combination group, the rates were 17.65% (6/34) and 10.34% (3/29), respectively. There was no statistically significant difference between the CD + BG group and the PRP combination group (P = 0.441), but both differed significantly from the control group (P < 0.001). Kaplan-Meier survival analysis showed that over time, the proportion of patients in the PRP combination group who did not require THA was consistently higher than that in the CD + BG group. Among patients who did not undergo THA, the proportion of Ficat-Arlet stage I-II patients in the PRP combination group was 88.46% (23/26), which was higher than the 64.29% (18/28) in the CD + BG group, showing a significant difference (P = 0.038). VAS score and HHS were compared between the two groups at 6 months, 12 months, and the last follow-up point, with patients in the PRP combination group showing better scores than those in the CD + BG group (p < 0.05) in both metrics. CONCLUSION The combination therapy of CD, BG, and PRP demonstrates significant advantages in improving symptoms and delaying disease progression in early-stage ANFH.
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Affiliation(s)
- Rong-Da Xu
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Si-Yu Duan
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Hai-Rui Liang
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Ming Sun
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Hang Wen
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Xue-Ting Zhou
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Han-Fei Liu
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China
| | - Zhen-Cun Cai
- Department of Orthopedics Surgery, Central Hospital Affiliated to Shenyang Medical College, 5 Nanqi West Road, Shenyang, Liaoning, 110024, China.
- Liaoning Province Key Laboratory for Phenomics of Human Ethnic Specificity and Critical Illness, Shenyang Key Laboratory for Phenomics, Shenyang Medical College, Shenyang, Liaoning, China.
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Yoon SD, Shim BJ, Baek SH, Kim SY. Implantation of Culture-Expanded Bone Marrow Derived Mesenchymal Stromal Cells for Treatment of Osteonecrosis of the Femoral Head. Tissue Eng Regen Med 2024; 21:929-941. [PMID: 38877362 PMCID: PMC11286925 DOI: 10.1007/s13770-024-00647-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 04/20/2024] [Accepted: 04/24/2024] [Indexed: 06/16/2024] Open
Abstract
BACKGROUND Although core decompression (CD) with stem cell for the treatment of osteonecrosis of the femoral head (ONFH) showed promising results in many reports, the efficacy remains uncertain. We aimed to evaluate the efficacy of CD with culture-expanded autologous bone marrow-derived mesenchymal stem cell (BM-MSC) implantation in early stage ONFH. METHODS A total of 18 patients (22 hips) with ONFH who underwent CD with culture-expanded BM-MSC implantation from September 2013 to July 2020 were retrospectively reviewed. The median age was 35.0 years [interquartile range (IQR), 28.5-42.0], and the median follow-up period was 4.0 years (IQR, 2.0-5.3). The median number of MSCs was 1.06 × 108. To evaluate radiographic and clinical outcomes, Association Research Circulation Osseous (ARCO) classifications, Japanese Investigation Committee classification, combined necrotic angle (CNA) visual analogue scale (VAS) and Harris Hip Score (HHS) were checked at each follow-up. RESULTS The preoperative stage of ONFH was ARCO 2 in 14 hips and ARCO 3a in 8 hips. The ARCO staging was maintained in 7 hips in ARCO 2 and 4 hips in ARCO 3a. The radiographic failure rate of ARCO 2 and 3a was 14.3 and 50%, respectively. Furthermore, CNA decreased to more than 20° in 6 hips (four were ARCO 2 and two were ARCO 3a).There was no significant difference in the VAS and HHS (P = 0.052 and P = 0.535, respectively). Total hip arthroplasty was performed in 4 hips. CONCLUSION CD with culture-expanded autologous BM-MSCs showed promising results for the treatment of early stage ONFH.
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Affiliation(s)
- Seong-Dae Yoon
- Department of Orthopedic Surgery, College of Medicine, Kyungpook National University, 130, Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea
- Department of Orthopedic Surgery, Kyungpook National University Hospital, 130, Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea
| | - Bum-Jin Shim
- Department of Orthopedic Surgery, Yeungnam University Hospital, College of Medicine, Yeungnam University, 170, Hyeonchung-ro, Nam-gu, Daegu, 42415, South Korea
| | - Seung-Hoon Baek
- Department of Orthopedic Surgery, College of Medicine, Kyungpook National University, 130, Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea
- Department of Orthopedic Surgery, Kyungpook National University Hospital, 130, Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea
| | - Shin-Yoon Kim
- Department of Orthopedic Surgery, College of Medicine, Kyungpook National University, 130, Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea.
- Department of Orthopedic Surgery, Kyungpook National University Hospital, 130, Dongdeok-Ro, Jung-Gu, Daegu, 41944, South Korea.
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Lin YC, Chen YJ, Fan TY, Chou PH, Lu CC. Effect of bone marrow aspiration concentrate and platelet-rich plasma combination in anterior cruciate ligament reconstruction: a randomized, prospective, double-blinded study. J Orthop Surg Res 2024; 19:4. [PMID: 38169406 PMCID: PMC10763110 DOI: 10.1186/s13018-023-04512-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 12/25/2023] [Indexed: 01/05/2024] Open
Abstract
BACKGROUND The effect of bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) combination in enhancing graft maturation and tendon-bone tunnel interfacial healing after anterior cruciate ligament (ACL) reconstruction remains unclear. We hypothesised that BMAC and PRP combination could lead to better clinical results and better graft maturation/interface healing than PRP alone or conventional ACL reconstruction without any other biologic augmentation. METHODS In this randomised double-blind prospective study, patients undergoing ACL reconstruction surgery were randomly assigned into three groups: (1) control group (without any biologic augmentation), (2) PRP treatment group, and (3) combined BMAC and PRP (BMAC + PRP) group. Moreover, they were evaluated using the clinical functional score, laxity examination, and magnetic resonance imaging (MRI) analysis. RESULTS No significant difference was observed in the improvement of functional scores among groups. However, laxity improvement at 24 weeks showed a significant difference with the BMAC + PRP group having the lowest laxity. MRI analysis showed no significant change in whole graft maturation among groups. In particular, the BMAC + PRP group showed delayed signal peak and higher graft signal at 24 weeks compared with the other two groups; however, the difference was not significant. With regard to tendon-bone interfacial healing, the BMAC + PRP group showed significantly wider tendon-bone interface in the femoral bone tunnel at 24 weeks compared with the other two groups. Moreover, the BMAC + PRP group showed significantly higher peri-tunnel edema signal in the femoral bone tunnel at 12 weeks compared with the other two groups. CONCLUSION PRP alone and BMAC and PRP combination showed limited enhancing effect in clinical function, graft maturation and tendon-bone interfacial healing compared with control (no additional treatment). When BMAC is used in ACL reconstruction, the possibility of greater inflammation in the early stage to graft maturation and bone tunnel healing should be considered.
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Affiliation(s)
- Yu-Chuan Lin
- Department of Orthopaedic Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Jen Chen
- Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tsang-Yu Fan
- Department of Orthopaedic Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Hsi Chou
- Department of Orthopaedic Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Chang Lu
- Department of Orthopaedic Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
- School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Department of Orthopaedic Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan.
- Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Franklin J, Pavithran PV, Sidharthan N, NV S, Abraham N, Menon VU, Nair V, Kumar H. Delayed diagnosis of plasma cell disorder-related Fanconi syndrome in young adults presenting as osteomalacia: report of two cases with normokalemia and normal haematological parameters at the time of presentation. ITALIAN JOURNAL OF MEDICINE 2023. [DOI: 10.4081/itjm.2023.1559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023] Open
Abstract
Adult-onset hypophosphatemic osteomalacia is rare and diagnosis is frequently delayed. Fanconi syndrome (FS) due to monoclonal gammopathy is a well-recognized, but rare cause of hypophosphatemia. The relatively young age of patients and normal routine hematological parameters often results in late recognition of this treatable disease entity. Low phosphorus, elevated alkaline phosphatase, mildly impaired renal function and hypokalemia are often the only abnormalities on routine evaluation. We summarize the clinico-pathological features of two cases who initially presented with fractures and proximal myopathy and were subsequently found to have FS secondary to light chain proximal tubulopathy. Atypical features like absence of hypokalemia at presentation and elevated Fibroblast Growth Factor 23(FGF 23), a marker of oncogenic osteomalacia were noted. Marked clinical improvement and recovery of renal parameters were evident with phosphate supplements and chemotherapy for the plasma cell disorder. FS due to monoclonal gammopathy may present with atypical features and diagnosis may be challenging
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Franklin J, Pavithran PV, Sidharthan N, NV S, Abraham N, Menon VU, Nair V, Kumar H. Delayed diagnosis of plasma cell disorder-related Fanconi syndrome in young adults presenting as osteomalacia: report of two cases with normokalemia and normal haematological parameters at the time of presentation. ITALIAN JOURNAL OF MEDICINE 2023. [DOI: 10.4081/itjm.2022.1559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Adult-onset hypophosphatemic osteomalacia is rare and diagnosis is frequently delayed. Fanconi syndrome (FS) due to monoclonal gammopathy is a well-recognized, but rare cause of hypophosphatemia. The relatively young age of patients and normal routine hematological parameters often results in late recognition of this treatable disease entity. Low phosphorus, elevated alkaline phosphatase, mildly impaired renal function and hypokalemia are often the only abnormalities on routine evaluation. We summarize the clinico-pathological features of two cases who initially presented with fractures and proximal myopathy and were subsequently found to have FS secondary to light chain proximal tubulopathy. Atypical features like absence of hypokalemia at presentation and elevated Fibroblast Growth Factor 23(FGF 23), a marker of oncogenic osteomalacia were noted. Marked clinical improvement and recovery of renal parameters were evident with phosphate supplements and chemotherapy for the plasma cell disorder. FS due to monoclonal gammopathy may present with atypical features and diagnosis may be challenging
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7
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Hoogervorst P, Campbell JC, Scholz N, Cheng EY. Core Decompression and Bone Marrow Aspiration Concentrate Grafting for Osteonecrosis of the Femoral Head. J Bone Joint Surg Am 2022; 104:54-60. [PMID: 35389906 DOI: 10.2106/jbjs.20.00527] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Core decompression (CD) with bone marrow aspiration concentrate (BMAC) is a technique that may improve outcomes in osteonecrosis of the femoral head (ONFH). The primary aim of this study was to evaluate the radiographic progression free survival (PFS) of CD augmented with BMAC. Secondary aims were to determine the survivorship with conversion (CFS) to total hip arthroplasty (THA) as an endpoint, determine prognostic factors, and characterize the cellular quality of the BMAC. METHODS A retrospective cohort study of 61 femoral heads (40 patients) was performed. Patient demographics, comorbidities, BMI, smoking status, etiology, location and extent of ONFH were recorded. The primary endpoint was radiographic progression of ONFH and secondarily, conversion to THA. Additional aims were to determine predictive factors for progression and report the cellular characteristics of the BMAC. Data obtained were compared to the results of a prior randomized controlled trial comparing CD alone versus CD with polymethylmethacrylate cement (PMMA) augmentation. RESULTS Radiographic PFS of CD with BMAC at 2 and 5 years was 78.3% and 53.3%, respectively. The risk of progression was lower in the CD with BMAC group compared to CD alone (HR0.45, p = 0.03), however this difference no longer remained statistically significant on multivariate analysis. Conversion to total hip arthroplasty free survival (CFS) of CD with BMAC at both 2 and 5 years was 72.1% and 54.6%, respectively with no differences compared to the control groups (CD alone, CD and PMMA). The predictive factors for progression were obesity (BMI ≥ 30) and the extent of the disease as quantified by either percentage involvement, necrotic index or modified necrotic index. CONCLUSIONS No differences in PFS or CFS between CD with BMAC compared to CD alone or CD with PMMA were identified. Independent statistically significant predictors of progression-free survival or conversion to THA are BMI ≥ 30 and the extent of ONFH. Further research with an adequately powered randomized controlled trial is needed. LEVEL OF EVIDENCE 3.
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Affiliation(s)
- Paul Hoogervorst
- Department of Orthopedic Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Joshua C Campbell
- Department of Orthopaedic Surgery, George Washington University, Washington, District of Columbia
| | - Natalie Scholz
- Department of Orthopedic Surgery, University of Minnesota, Minneapolis, Minnesota
| | - Edward Y Cheng
- Department of Orthopedic Surgery, University of Minnesota, Minneapolis, Minnesota
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Houdek MT, Wyles CC, Smith JRH, Terzic A, Behfar A, Sierra RJ. Hip decompression combined with bone marrow concentrate and platelet-rich plasma for corticosteroid-induced osteonecrosis of the femoral head : mid-term update from a prospective study. Bone Jt Open 2021; 2:926-931. [PMID: 34751583 PMCID: PMC8636295 DOI: 10.1302/2633-1462.211.bjo-2021-0132.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Aims Bone marrow-derived mesenchymal stem cells obtained from bone marrow aspirate concentrate (BMAC) with platelet-rich plasma (PRP), has been used as an adjuvant to hip decompression. Early results have shown promise for hip preservation in patients with osteonecrosis (ON) of the femoral head. The purpose of the current study is to examine the mid-term outcome of this treatment in patients with precollapse corticosteroid-induced ON of the femoral head. Methods In all, 22 patients (35 hips; 11 males and 11 females) with precollapse corticosteroid-induced ON of the femoral head underwent hip decompression combined with BMAC and PRP. Mean age and BMI were 43 years (SD 12) and 31 kg/m² (SD 6), respectively, at the time of surgery. Survivorship free from femoral head collapse and total hip arthroplasty (THA) and risk factors for progression were evaluated at minimum five-years of clinical follow-up with a mean follow-up of seven years (5 to 8). Results Survivorship free from femoral head collapse and THA for any reason was 84% and 67% at seven years postoperatively, respectively. Risk factors for conversion to THA included a high preoperative modified Kerboul angle (grade 3 or 4) based on preoperative MRI (hazard ratio (HR) 3.96; p = 0.047) and corticosteroid use at the time of decompression (HR 4.15; p = 0.039). The seven-year survivorship for patients with grade 1 or 2 Kerboul angles for conversion to THA for articular collapse, and THA for any reason, were 96% and 72%, respectively, versus THA for articular collapse and THA for any reason in patients with grade 3 or 4 Kerboul angles of 40% (p = 0.003) and 40% (p = 0.032). Conclusion At seven years, hip decompression augmented with BMAC and PRP provided a 67% survivorship free from THA in patients with corticosteroid-induced ON. Ideal candidates for this procedure are patients with low preoperative Kerboul angles and can stop corticosteroid treatment prior to decompression. Cite this article: Bone Jt Open 2021;2(11):926–931.
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Affiliation(s)
| | - Cody C Wyles
- Ortho Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | | | - Andre Terzic
- Orthopaedic Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Atta Behfar
- Orthopaedic Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Rafael J Sierra
- Ortho Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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El-Jawhari JJ, Ganguly P, Jones E, Giannoudis PV. Bone Marrow Multipotent Mesenchymal Stromal Cells as Autologous Therapy for Osteonecrosis: Effects of Age and Underlying Causes. Bioengineering (Basel) 2021; 8:69. [PMID: 34067727 PMCID: PMC8156020 DOI: 10.3390/bioengineering8050069] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 04/29/2021] [Accepted: 05/13/2021] [Indexed: 12/21/2022] Open
Abstract
Bone marrow (BM) is a reliable source of multipotent mesenchymal stromal cells (MSCs), which have been successfully used for treating osteonecrosis. Considering the functional advantages of BM-MSCs as bone and cartilage reparatory cells and supporting angiogenesis, several donor-related factors are also essential to consider when autologous BM-MSCs are used for such regenerative therapies. Aging is one of several factors contributing to the donor-related variability and found to be associated with a reduction of BM-MSC numbers. However, even within the same age group, other factors affecting MSC quantity and function remain incompletely understood. For patients with osteonecrosis, several underlying factors have been linked to the decrease of the proliferation of BM-MSCs as well as the impairment of their differentiation, migration, angiogenesis-support and immunoregulatory functions. This review discusses the quality and quantity of BM-MSCs in relation to the etiological conditions of osteonecrosis such as sickle cell disease, Gaucher disease, alcohol, corticosteroids, Systemic Lupus Erythematosus, diabetes, chronic renal disease and chemotherapy. A clear understanding of the regenerative potential of BM-MSCs is essential to optimize the cellular therapy of osteonecrosis and other bone damage conditions.
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Affiliation(s)
- Jehan J El-Jawhari
- Department of Biosciences, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK
- Clinical Pathology Department, Mansoura University, Mansoura 35516, Egypt
| | - Payal Ganguly
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; (P.G.); (E.J.); (P.V.G.)
| | - Elena Jones
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; (P.G.); (E.J.); (P.V.G.)
| | - Peter V Giannoudis
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds, Leeds LS2 9JT, UK; (P.G.); (E.J.); (P.V.G.)
- Academic Department of Trauma and Orthopedic, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
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10
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Woodell-May J, Steckbeck K, King W. Potential Mechanism of Action of Current Point-of-Care Autologous Therapy Treatments for Osteoarthritis of the Knee-A Narrative Review. Int J Mol Sci 2021; 22:ijms22052726. [PMID: 33800401 PMCID: PMC7962845 DOI: 10.3390/ijms22052726] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/21/2021] [Accepted: 02/23/2021] [Indexed: 12/13/2022] Open
Abstract
Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.
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Affiliation(s)
| | | | - William King
- Owl Manor, 720 East Winona Avenue, Warsaw, IN 46580, USA;
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11
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Lana JFSD, da Fonseca LF, Macedo RDR, Mosaner T, Murrell W, Kumar A, Purita J, de Andrade MAP. Platelet-rich plasma vs bone marrow aspirate concentrate: An overview of mechanisms of action and orthobiologic synergistic effects. World J Stem Cells 2021; 13:155-167. [PMID: 33708344 PMCID: PMC7933989 DOI: 10.4252/wjsc.v13.i2.155] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Revised: 12/15/2020] [Accepted: 01/15/2021] [Indexed: 02/06/2023] Open
Abstract
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
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Affiliation(s)
| | | | - Rafael da Rocha Macedo
- Department of Orthopedics, Rede D’Or Unit IFOR Hospital, São Bernardo do Campo 09715-021, SP, Brazil
| | - Tomas Mosaner
- Department of Orthopedics, The Bone and Cartilage Institute, Indaiatuba 13334-170, SP, Brazil
| | - William Murrell
- Department of Orthopaedics, Healthpoint UAE, Abu Dhabi 00000, United Arab Emirates
| | - Ashok Kumar
- Department of Orthopaedics, My Doc Specialist Medical Centre, Dubai 00000, United Arab Emirates
| | - Joseph Purita
- Department of Orthopedics, Institute of Regenerative Medicine, Boca Raton, FL 33432, United States
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12
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Ando W, Sakai T, Fukushima W, Kaneuji A, Ueshima K, Yamasaki T, Yamamoto T, Nishii T, Sugano N. Japanese Orthopaedic Association 2019 Guidelines for osteonecrosis of the femoral head. J Orthop Sci 2021; 26:46-68. [PMID: 33388233 DOI: 10.1016/j.jos.2020.06.013] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 06/04/2020] [Accepted: 06/05/2020] [Indexed: 12/20/2022]
Abstract
PURPOSE The Clinical Practice Guidelines for Osteonecrosis of the Femoral Head (ONFH) 2019 Edition, written by the working group for ONFH guidelines of the Japanese Investigation Committee (JIC) for ONFH under the auspices of the Japanese Ministry of Health, Labour, and Welfare and endorsed by the Japanese Orthopaedic Association, were published in Japanese in October 2019. The objective of this guideline is to provide a support tool for decision-making between doctors and patients. METHODS Procedures for developing this guideline were based on the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014, which proposed an appropriate method for preparing clinical guidelines in Japan. RESULTS This clinical practice guideline consists of 7 chapters: epidemiology; pathology; diagnosis; conservative therapy; surgical treatment: bone transplantation/cell therapy; surgical treatment: osteotomy; and surgical treatment: hip replacement. Twelve background questions and 13 clinical questions were determined to define the basic features of the disease and to be addressed when deciding treatment in daily practice, respectively. CONCLUSIONS The clinical practice guidelines for the ONFH 2019 edition will be useful for physicians, investigators, and medical staff in clinical practice, as well as for patients, during the decision-making process when defining how to treat ONFH.
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Affiliation(s)
- Wataru Ando
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takashi Sakai
- Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
| | - Wakaba Fukushima
- Department of Public Health, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Ayumi Kaneuji
- Department of Orthopaedic Surgery, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan
| | - Keiichiro Ueshima
- Department of Orthopaedic Surgery, Kyoto Interdisciplinary Institute Hospital of Community Medicine, Kyoto, Kyoto, Japan
| | - Takuma Yamasaki
- Department of Orthopaedic Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Hiroshima, Japan
| | - Takuaki Yamamoto
- Department of Orthopaedic Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Fukuoka, Japan
| | - Takashi Nishii
- Department of Orthopaedic Surgery, Osaka General Medical Center, Osaka, Osaka, Japan
| | | | - Nobuhiko Sugano
- Department of Orthopaedic Medical Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
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13
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Kuroda Y, Ito-Ihara T, Abe H, Nankaku M, Okuzu Y, Kawai T, Goto K, Matsuda S. Recombinant human FGF-2 therapy for osteonecrosis of the femoral head: 5-year follow-up. Regen Med 2020; 15:2261-2271. [DOI: 10.2217/rme-2020-0148] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To evaluate the 5-year outcomes from the prospective study of recombinant human FGF-2 (rhFGF-2) for osteonecrosis of the femoral head (ONFH). Methods: Ten patients (average age 39.8 years) with nontraumatic, precollapse ONFH were percutaneously administered with 800 μg rhFGF-2 contained in gelatin hydrogel. Radiological changes and the prevalidated Harris hip score (HHS), visual analogue scale for pain and University of California, Los Angeles activity-rating scale scoring systems were evaluated. Results: The 5-year comparison in type C2 showed higher joint preservation in the rhFGF-2 group (71.4%) than in the natural course group (15.4%). Two of three clinical scores (Harris hip score and visual analogue scale for pain) improved significantly. Postoperative MRI demonstrated significant reduction in ONFH size. There were no adverse events. Conclusion: rhFGF-2 treatment for ONFH appears to be safe and effective and may have the potential to prevent disease progression.
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Affiliation(s)
- Yutaka Kuroda
- Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
| | - Toshiko Ito-Ihara
- Department of Clinical Innovative Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hiroyasu Abe
- Department of Biomedical Statistics & Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Manabu Nankaku
- Rehabilitation Unit, Kyoto University Hospital, Kyoto, Japan
| | - Yaichiro Okuzu
- Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
| | - Toshiyuki Kawai
- Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
| | - Koji Goto
- Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
| | - Shuichi Matsuda
- Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Shogoin, Kawahara-cho 54, Sakyo-ku, Kyoto 606-8507, Japan
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Elgaz S, Bonig H, Bader P. Mesenchymal stromal cells for osteonecrosis. J Transl Med 2020; 18:399. [PMID: 33081809 PMCID: PMC7576732 DOI: 10.1186/s12967-020-02565-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 10/10/2020] [Indexed: 12/24/2022] Open
Abstract
Osteonecrosis (ON) is an acquired debilitating skeletal disorder, which is caused by a multitude of traumatic and non-traumatic etiological factors. Vascular damage, mechanical stress and increased intraosseous pressure have been discussed as contributors to ON. The optimal treatment of ON remains to be determined, since the current gold standard, core decompression, is insufficiently effective. Specific properties of mesenchymal stromal cells (MSCs) provide the rationale for their assessment in advanced stages of ON: Osteoinductive potential has been demonstrated and MSC preparations of suitable quality for use as medicinal products have been developed. Here we review the scant information on the use of allogeneic or autologous MSCs in advanced ON as well as potentially supportive data from pre-clinical studies with autologous bone marrow mononuclear cells (auto BM-MNCs), which have been studied quite extensively and the presumed therapeutic effect of which was attributed to the rare MSCs contained in these cell products. Outcomes in clinical trials with MSCs and auto-BM-MNCs remain preliminary and non-definitive, at best promising, with respect to their pharmacological effect. Clearly, though, the application of any of these cell therapies was technically feasible and safe in that it was associated with low complication rates. The heterogeneity of cell type and source, study protocols, cell manufacturing, cell properties, cell doses and surgical techniques might contribute to inconsistent results.
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Affiliation(s)
- S Elgaz
- Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany
| | - H Bonig
- Institute of Transfusion Medicine and Immunohematology, and German Red Cross Blood Center Baden-Württemberg-Hessen, Goethe University, Frankfurt am Main, Germany
| | - P Bader
- Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
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Kumar P, Shetty VD, Dhillon MS. Efficacy of orthobiologic adjuvants to core decompression for hip preservation in avascular necrosis hip. J Hip Preserv Surg 2020; 7:423-438. [PMID: 33948198 PMCID: PMC8081433 DOI: 10.1093/jhps/hnaa051] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Revised: 08/17/2020] [Indexed: 01/12/2023] Open
Abstract
Head preserving modalities in avascular necrosis (AVN) hip are variably effective in early stages, and further options that could prevent head distortion and osteoarthritis are needed. Core decompression (CD) is the most commonly used surgery in the early stages of osteonecrosis with variable rates of success. The present review aimed to determine the effectiveness of bone marrow aspirate concentrate (BMAC), platelet-rich plasma (PRP), bone morphogenetic proteins (BMP) or their combination with CD in early stages of AVN hip, prior to collapse of femoral head. Additionally, any newer unexplored modalities were also searched for and ascertained. PubMed and SCOPUS databases were searched for relevant articles in English language describing CD with aforementioned orthobiologics. We analysed a total of 20 studies published between 2011 and 2020. There were 6 retrospective and 14 prospective studies. PRP showed improved survival and functional outcomes; however, with only three studies, there is inconclusive evidence for its routine utilization. BMAC enhances the efficacy of CD which can further be increased by culture and expansion of cells or combining it with PRP to stimulate growth. In conclusion, CD with BMAC works more efficiently than CD alone prior to collapse of femoral head in AVN. However, PRP needs more evidence for extensive application. Addition of PRP to BMAC or culturing the latter could further enhance the potency of CD + BMAC combination. Very limited data is available for the efficacy of BMP-7 and the role of intraosseous bisphosphonates should be evaluated for a cheaper and potential alternative.
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Affiliation(s)
- Prasoon Kumar
- Department of Orthopaedics, PGIMER, Chandigarh 160012, India
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Zhao D, Liu Y, Ma C, Gu G, Han DF. A Mini Review: Stem Cell Therapy for Osteonecrosis of the Femoral Head and Pharmacological Aspects. Curr Pharm Des 2020; 25:1099-1104. [PMID: 31131747 DOI: 10.2174/1381612825666190527092948] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 05/14/2019] [Indexed: 01/07/2023]
Abstract
Osteonecrosis of the femoral head (ONFH) is a common disease that occurs frequently. Due to various etiologies, the blood supply directed to the femoral head is interrupted in patients with ONFH. This disease can result in degeneration and necrosis of the subchondral bone of the femoral head, which ultimately cause a collapse of the femoral head. Of note, ONFH can extremely affect the quality of living of patients with a high disability rate. Also, this disease often includes middle-aged and younger people. However, effective treatments of ONFH are still challenging in clinics. In recent years, stem cells have been profoundly studied and a relevant new technology has been developed rapidly and applied for regenerative medicine. A number of reports have demonstrated successful results of the treatment of ONFH by using stem cell transplantation. By the combination of minimally invasive hip decompression and injection of mesenchymal stem cells into the necrotic lesion, the retrospective analysis of patients treated revealed that significant pain relief was observed in 86% patients and they had no major complications after treatment. Thus, stem cell transplantation is anticipated to be applied as an innovative approach in the treatment of ONFH. This review will summarize results obtained from recent human and animal studies, which include the pathophysiological process of ONFH, current techniques and effects of using stem cells on the treatment of ONFH together with pharmacological aspects. Overall, the current evidence reveals the treatment of ONFH using stem cell technology as promising. Nonetheless, additional in-depth studies are necessary to better explore the application of this technology and seek more ideal approaches to minimize difficulties related to stem cells.
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Affiliation(s)
- Ding Zhao
- Department of Orthopedics, First Hospital of Jilin University, Changchun, China
| | - Yijun Liu
- Department of Orthopedics, First Hospital of Jilin University, Changchun, China
| | - Chi Ma
- Department of Neurosurgery, First Hospital of Jilin University, Changchun, China
| | - Guishan Gu
- Department of Orthopedics, First Hospital of Jilin University, Changchun, China
| | - Dong-Feng Han
- Department of Emergency Medicine, First Hospital of Jilin University, Changchun, China
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Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials. J Clin Med 2020; 9:jcm9010139. [PMID: 31947922 PMCID: PMC7019836 DOI: 10.3390/jcm9010139] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 12/21/2019] [Accepted: 01/02/2020] [Indexed: 01/01/2023] Open
Abstract
The deterioration of the human skeleton's capacity for self-renewal occurs naturally with age. Osteoporosis affects millions worldwide, with current treatments including pharmaceutical agents that target bone formation and/or resorption. Nevertheless, these clinical approaches often result in long-term side effects, with better alternatives being constantly researched. Mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue are known to hold therapeutic value for the treatment of a variety of bone diseases. The following review summarizes the latest studies and clinical trials related to the use of MSCs, both individually and combined with other methods, in the treatment of a variety of conditions related to skeletal health. For example, some of the most recent works noted the advantage of bone grafts based on biomimetic scaffolds combined with MSC and growth factor delivery, with a greatly increased regeneration rate and minimized side effects for patients. This review also highlights the continuing research into the mechanisms underlying bone homeostasis, including the key transcription factors and signalling pathways responsible for regulating the differentiation of osteoblast lineage. Paracrine factors and specific miRNAs are also believed to play a part in MSC differentiation. Furthering the understanding of the specific mechanisms of cellular signalling in skeletal remodelling is key to incorporating new and effective treatment methods for bone disease.
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Wang P, Li G, Qin W, Shi B, Liu FJ, Wang LL, Zhao BN, Sun TF, Lin L, Wang DD. Repair of osteonecrosis of the femoral head : 3D printed Cervi cornus Colla deproteinized bone scaffolds. DER ORTHOPADE 2019; 48:213-223. [PMID: 30656386 PMCID: PMC6449326 DOI: 10.1007/s00132-018-03678-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Background Osteonecrosis of the femoral head (ONFH) is a common joint disease and a major cause of morbidity. Objective In this study Cervi cornus Colla (CCC) deproteinized bone scaffolds were designed and three dimensional (3D)-printed for the repair of ONFH in rats. Material and methods The CCC-deproteinized bone scaffolds were 3D-printed using polycaprolactone mixed with the CCC-deproteinized bone powder. The scaffolds were viewed under a scanning electron microscope and subjected to compression analysis. Osteoblasts were isolated from rats and coated onto the scaffolds. Cell proliferation assays were performed with the MTT (3‑[4,5-dimethylthiazole‑2]-2,5-diphenyltetrazolium bromide) kit from Promega. An ONFH was induced in rats and a CCC-deproteinized bone scaffold was implanted into the necrotic femoral head. General observations, X‑ray imaging, and pathological examination of the femoral head were performed to evaluate the treatment of ONFH in the rats. Results The scaffolds were porous with a mean pore diameter of 315.70 ± 41.52 nm and a porosity of 72.86 ± 5.45% and exhibited favorable mechanical properties and degradation. In vitro assays showed that osteoblasts accumulated in the pores and adhered to the scaffolds. The CCC-deproteinized bone scaffolds enhanced the proliferation of osteoblasts. The in vivo experiments revealed that the general observation score of rats in the CCC-scaffold implanted group was significantly higher than that in the control group. The X‑ray images showed significant alleviation of ONFH in the CCC-deproteinized bone scaffold implanted rats. The femoral heads of rats in the treatment group showed less destruction or ossification of cartilage cells, few bone cement lines, very little necrosis or irregularities on the cartilage surface and only a small amount of inflammatory cell infiltration in the medullary cavity. Conclusion These results suggest that CCC-deproteinized bone scaffold implants facilitated the repair of ONFH in rats. This research provides a new therapeutic approach for the repair of early and mid-term ONFH.
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Affiliation(s)
- Ping Wang
- State Key Laboratory of Precision Measurement Technology and Instruments, Tianjin University, 300072, Tianjin, China
- Shandong Academy of Chinese Medicine, 250014, Jinan, China
| | - Gang Li
- State Key Laboratory of Precision Measurement Technology and Instruments, Tianjin University, 300072, Tianjin, China
| | - Wen Qin
- Shandong University Hospital, 250100, Jinan, China
| | - Bin Shi
- Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, 250062, Jinan, China.
| | - Fan-Jie Liu
- Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, 250062, Jinan, China
| | - Lei-Lei Wang
- Key Laboratory for Applied Microbiology of Shandong Province, Ecology Institute of Shandong Academy of Sciences, 250014, Jinan, China
| | - Bo-Nian Zhao
- Shandong Academy of Chinese Medicine, 250014, Jinan, China
| | - Tie-Feng Sun
- Shandong Academy of Chinese Medicine, 250014, Jinan, China
| | - Ling Lin
- State Key Laboratory of Precision Measurement Technology and Instruments, Tianjin University, 300072, Tianjin, China.
| | - Dan-Dan Wang
- Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, 250062, Jinan, China.
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Zhou W, Qu M, Lv Y, Zhu J. New Advances in Stem Cell Therapy for Osteonecrosis of the Femoral Head. Curr Stem Cell Res Ther 2019; 14:226-229. [PMID: 30360727 DOI: 10.2174/1574888x13666181025120252] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Revised: 09/26/2018] [Accepted: 09/29/2018] [Indexed: 02/07/2023]
Abstract
Osteonecrosis of the femoral head (ONFH) is a common refractory orthopedic disease with multiple etiologies that more frequently occurs in middle-aged and young people. ONFH is the main cause of hip replacement in young patients. Since Professor Hernigou first reported the use of stem cells in the treatment of early stage ONFH, a large number of studies have demonstrated the potential of stem cells in the treatment of adult patients with ONFH. With the rise of interdisciplinary stem cell therapy combined with platelet-rich plasma therapy, gene therapy or other methods have gradually attracted the attention of researchers. This article summarizes the current advances in stem cell therapy for ONFH, as well as the problems and challenges, which may provide reference for further research.
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Affiliation(s)
- Wei Zhou
- Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province 610036, China
| | - Ming Qu
- Department of Orthopaedics, Fuping Couty Hospital, Fuping, Shaanxi Province, 711700, China
| | - Yajie Lv
- Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 71000, China
| | - Jinyu Zhu
- Institute of Orthopaedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 71000, China.,Department of Orthopaedics, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, Guangdong Province 518055, China
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Hao YQ, Guo H, Zhu T, Xu ZC, Qi HD, Lu C, Yuan PW. Core decompression, lesion clearance and bone graft in combination with Tongluo Shenggu decoction for the treatment of osteonecrosis of the femoral head: A retrospective cohort study. Medicine (Baltimore) 2018; 97:e12674. [PMID: 30313059 PMCID: PMC6203527 DOI: 10.1097/md.0000000000012674] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The aim of this study was to evaluate the clinical effect of core decompression (CD), lesion clearance, and bone graft in combination with Tongluo Shenggu decoction for the treatment of osteonecrosis of the femoral head (ONFH).A total of 75 patients (92 hips), with ONFH at Association Research Circulation Osseous (ARCO) stages II to IIIA, were studied and divided into treatment group and control group. In control group, patients were treated with the CD in combination with autologous or artificial ceramic bone graft. In treatment group, patients were treated with the above method combined with Tongluo Shenggu decoction. Patients were followed-up at 1 month, 6 months, and 24 months after surgery. The visual analogue scale (VAS) scores, Harris Hip Score (HSS), and total effective rates were measured and recorded.The total effective rate of the treatment group was significantly higher than that of the control group (97.2% vs. 89.9%, P < .05). Compared with preoperative, the VAS and HSS scores were both improved at final follow-up, and there was significant difference between 2 groups (P < .01).The combination of CD, lesion clearance, and the bone graft with Tongluo Shenggu decoction is safe and effective for the treatment of ONFH, owing to which it can provide higher postoperative functional outcomes, reduce pain, and achieve smaller osteonecrosis area and better bone changes.
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Affiliation(s)
- Yang-Quan Hao
- Department of osteonecrosis and joint reconstruction, Honghui Hospital, Xi’an Jiaotong University, Xi’an
| | - Hao Guo
- Department of osteonecrosis and joint reconstruction, Honghui Hospital, Xi’an Jiaotong University, Xi’an
| | - Tian Zhu
- Graduate School, Shaanxi university of Chinese medicine, Shiji Ave, Xi’an-xianyang New Ecomic Zone
| | - Zhao-Chen Xu
- Graduate School, Shaanxi university of Chinese medicine, Shiji Ave, Xi’an-xianyang New Ecomic Zone
| | - Han-Deng Qi
- Graduate School, Shaanxi university of Chinese medicine, Shiji Ave, Xi’an-xianyang New Ecomic Zone
| | - Chao Lu
- Department of osteonecrosis and joint reconstruction, Honghui Hospital, Xi’an Jiaotong University, Xi’an
| | - Pu-Wei Yuan
- Department of Orthopedics, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shanxi Province, P.R. China
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Andriolo L, Merli G, Tobar C, Altamura SA, Kon E, Filardo G. Regenerative therapies increase survivorship of avascular necrosis of the femoral head: a systematic review and meta-analysis. INTERNATIONAL ORTHOPAEDICS 2018; 42:1689-1704. [PMID: 29411077 DOI: 10.1007/s00264-018-3787-0] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 01/18/2018] [Indexed: 02/08/2023]
Abstract
PURPOSE The aim of this study was to document the available evidence on the use of regenerative techniques for the treatment of femoral head osteonecrosis (or avascular necrosis of femoral head, AVN) and to understand their benefit compared to core decompression (CD) alone in avoiding failure and the need for total hip replacement (THR). METHODS The search was conducted on three medical electronic databases according to PRISMA guidelines. The studies reporting number and timing of failures were included in a meta-analysis calculating cumulative survivorship with a Kaplan-Mayer curve. Moreover, the results on failures in treatment groups reported in RCT were compared with those documented in control groups, in order to understand the benefit of biological therapies compared to CD for the treatment of AVN. RESULTS Forty-eight studies were included in this systematic review, reporting results of different types of regenerative techniques: mesenchymal stem cell implantation in the osteonecrotic area, intra-arterial infiltration with mesenchymal stem cells, implantation of bioactive molecules, or platelet-rich plasma. Overall, reported results were good, with a cumulative survivorship of 80% after ten year follow-up, and better results when regenerative treatments were combined to CD compared to CD alone (89.9% vs 70.6%, p < 0.0001). CONCLUSION Regenerative therapies offer good clinical results for the treatment of AVN. The combination of CD with regenerative techniques provides a significant improvement in terms of survivorship over time compared with CD alone. Further studies are needed to identify the best procedure and the most suitable patients to benefit from regenerative treatments for AVN.
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Affiliation(s)
- Luca Andriolo
- II Orthopaedic and Traumatologic Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
| | - Giulia Merli
- Nano-Biotechnology Laboratory-NaBi, Research and Innovation Technology Department, Bologna, Italy.
| | - Carlos Tobar
- Department of Orthopedics and Traumatology, Avansalud Clinic of Santiago, Santiago, Chile
| | | | - Elizaveta Kon
- Humanitas University Department of Biomedical Sciences, Milan, Italy
- Humanitas Clinical and Research Center, Milan, Italy
| | - Giuseppe Filardo
- Nano-Biotechnology Laboratory-NaBi, Research and Innovation Technology Department, Bologna, Italy
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22
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Reply to the Letter to the Editor: Stem Cells Combined With Platelet-rich Plasma Effectively Treat Corticosteroid-induced Osteonecrosis of the Hip: A Prospective Study. Clin Orthop Relat Res 2018; 476:1129-1130. [PMID: 29601399 PMCID: PMC5916597 DOI: 10.1007/s11999.0000000000000284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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23
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Murray IR, Robinson PG, West CC, Goudie EB, Yong LY, White TO, LaPrade RF. Reporting Standards in Clinical Studies Evaluating Bone Marrow Aspirate Concentrate: A Systematic Review. Arthroscopy 2018; 34:1366-1375. [PMID: 29395555 DOI: 10.1016/j.arthro.2017.11.036] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 11/28/2017] [Accepted: 11/29/2017] [Indexed: 02/02/2023]
Abstract
PURPOSE To perform a systematic review of clinical studies evaluating bone marrow aspirate concentrate (BMAC) in the treatment of musculoskeletal pathology to compare levels of reporting with recently published minimum standards. METHODS A systematic review of the clinical literature from August 2002 to August 2017 was performed. Human clinical studies published in English and involving the administration of BMAC for musculoskeletal applications were included. Studies evaluating non-concentrated preparations of bone marrow aspirate or preparations of laboratory cultured cells were excluded. Studies evaluating the treatment of dental or maxillofacial conditions were excluded. Similarly, in vitro studies, editorials, letters to the editor, and reviews were excluded. Levels of reporting were compared with previously published minimum standards agreed on through an international Delphi consensus process. RESULTS Of 1,580 studies identified on the initial search, 46 satisfied the criteria for inclusion. Considerable deficiencies in reporting of key variables including the details of BMAC preparation and composition were noted. Studies reported information on only 42% (range, 25%-60%) of the variables included within established minimum reporting standards. No study provided adequate information to enable the precise replication of preparation protocols and accurate characterization of the BMAC formulation delivered. CONCLUSIONS We found that all existing clinical studies in the literature evaluating BMAC for orthopaedic or sports medicine applications are limited by inadequate reporting of both preparation protocols and composition. Deficient reporting of the variables that may critically influence outcomes precludes interpretation, prevents other researchers from reproducing experimental conditions, and makes comparisons across studies difficult. We encourage the adoption of emerging minimum reporting standards for clinical studies evaluating the use of mesenchymal stem cells in orthopaedics. LEVEL OF EVIDENCE Level IV, systematic review of Level I through IV studies.
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Affiliation(s)
- Iain R Murray
- University of Edinburgh, Edinburgh, Scotland; Royal Infirmary of Edinburgh, Edinburgh, Scotland
| | | | | | | | - Li Y Yong
- University of Edinburgh, Edinburgh, Scotland
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Piuzzi NS, Hussain ZB, Chahla J, Cinque ME, Moatshe G, Mantripragada VP, Muschler GF, LaPrade RF. Variability in the Preparation, Reporting, and Use of Bone Marrow Aspirate Concentrate in Musculoskeletal Disorders: A Systematic Review of the Clinical Orthopaedic Literature. J Bone Joint Surg Am 2018; 100:517-525. [PMID: 29557869 DOI: 10.2106/jbjs.17.00451] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Interest in the therapeutic potential of bone marrow aspirate concentrate (BMAC) has grown exponentially. However, comparisons among studies and their processing methods are challenging because of inconsistent reporting of protocols, as well as poor characterization of the composition of the initial bone marrow aspirate and of the final products delivered. The purpose of this study was to perform a systematic review of the literature to evaluate the level of reporting related to the protocols used for BMAC preparation and the composition of BMAC utilized in the treatment of musculoskeletal diseases in published clinical studies. METHODS A systematic review of the literature was performed by searching PubMed, MEDLINE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials from 1980 to 2016. Inclusion criteria were human clinical trials, English language, and manuscripts that reported on the use of BMAC in musculoskeletal conditions. RESULTS After a comprehensive review of the 986 identified articles, 46 articles met the inclusion criteria for analysis. No study provided comprehensive reporting that included a clear description of the preparation protocol that could be used by subsequent investigators to repeat the method. Only 14 (30%) of the studies provided quantitative metrics of the composition of the BMAC final product. CONCLUSIONS The reporting of BMAC preparation protocols in clinical studies was highly inconsistent and studies did not provide sufficient information to allow the protocol to be reproduced. Moreover, comparison of the efficacy and yield of BMAC products is precluded by deficiencies in the reporting of preparation methods and composition. Future studies should contain standardized and stepwise descriptions of the BMAC preparation protocol, and the composition of the BMAC delivered, to permit validating and rationally optimizing the role of BMAC in musculoskeletal care.
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Affiliation(s)
- Nicolas S Piuzzi
- Department of Orthopaedic Surgery and Bioengineering, Cleveland Clinic, Cleveland, Ohio.,Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | | | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado
| | - Mark E Cinque
- Steadman Philippon Research Institute, Vail, Colorado
| | - Gilbert Moatshe
- Steadman Philippon Research Institute, Vail, Colorado.,Oslo University Hospital, University of Oslo, Oslo, Norway.,OSTRC, The Norwegian School of Sports Sciences, Oslo, Norway
| | | | - George F Muschler
- Department of Orthopaedic Surgery and Bioengineering, Cleveland Clinic, Cleveland, Ohio
| | - Robert F LaPrade
- Steadman Philippon Research Institute, Vail, Colorado.,The Steadman Clinic, Vail, Colorado
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Abstract
INTRODUCTION Core decompression (CD) with or without the addition of autologous bone graft (CDBG) is currently the most widely accepted treatment for hip osteonecrosis in stages of pre-collapse. The use of bone marrow mesenchymal stem cells (CDSC) is emerging as a promising biological alternative. We sought to determine the total hip arthroplasty (THA) conversion rate for patients treated with CD, CDBG or CDSC. MATERIAL AND METHODS Between 1996 and 2012, 97 cases were evaluated in 72 patients: 47 CD cases, 34 CDGB cases and 16 CDSC cases. The mean age was 39 (20-63) years, 25 bilateral, 19 female and 53 male, 14 Ficat 1 and 83 Ficat 2. Bilateral cases with asymmetric stage and equal treatment were excluded. RESULTS Conversion rate to THA was 44% for the CD group (21/47) at an average of 77 (24-324) months; 50% for the CDBG group (17/34) at an average of 34 (24-240) months and 50% for the CDSC group (8/16) at an average of 48 (24-72) months (p = 0.619). Log Rank test for survivorship analysis was not significant (p = 0.2011). Immunodeficiency or corticosteroid treatment history was associated with 16/47 of the CD group, 7/34 in the CDBG group and 1/16 in the CDSC group. Trauma was associated with 2/47 of the CD group, 5/34 of the CDBG group and none of the CDSC group. Hazard ratio considering risk factors was not significant (p = 0.252). CONCLUSIONS In these series of cases including patients with pre-collapse osteonecrosis, we observed non-significant results regarding rate of conversion to THA with CD, CDBG or CDSC at an average of 5.5 years.
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26
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Houdek MT, Wyles CC, Collins MS, Howe BM, Terzic A, Behfar A, Sierra RJ. Stem Cells Combined With Platelet-rich Plasma Effectively Treat Corticosteroid-induced Osteonecrosis of the Hip: A Prospective Study. Clin Orthop Relat Res 2018; 476. [PMID: 29529674 PMCID: PMC6259717 DOI: 10.1007/s11999.0000000000000033] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Randomized trials have shown the benefits of injecting bone marrow-derived mesenchymal stem cells (BmMSCs) after standard hip decompression in patients with osteonecrosis of the femoral head. However, the combination of BmMSCs and platelet-rich plasma (PRP) injected into the femoral head after decompression has not been reported previously. This study reports the results in a preliminary series of patients with osteonecrosis of the femoral head treated with BmMSCs plus PRP. QUESTIONS/PURPOSES (1) What is the survivorship free from reoperation, hip arthroplasty, and femoral head collapse in a preliminary series of patients with osteonecrosis of the femoral head treated with BmMSCs plus PRP? (2) Is there a change in the degree of femoral head involvement based on modified Kerboul angle? (3) What were the scores observed for pain and function at last followup? (4) Was there a difference in survivorship free from reoperation as a function of in vitro MSC count and viability? METHODS Twenty-two consecutive patients (35 hips; 11 men and 11 women) with corticosteroid-induced osteonecrosis who met study inclusion criteria were enrolled; none declined participation, and none was lost to followup, although one patient (two hips) died within a year of the procedure for reasons unrelated to it, and five patients (seven hips) did not undergo MRI at the 1-year followup. All patients had precollapse osteonecrosis, rated either University of Pennsylvania Stage 1 (n = 4) or Stage 2 (n = 31 hips). Mean age and body mass index were 43 years and 31 kg/m, respectively. Patients underwent pre- and postoperative radiographs and MRI to assess femoral head involvement using the modified Kerboul angle. Absolute cell count and colony-forming unit (CFU) assays were used to assess MSC abundance and viability of the bone marrow obtained at the time of surgery. Patients were followed at regular intervals to assess clinical response to treatment with a mean followup of 3 years (range, 2-4 years). The change in femoral head involvement was assessed with the modified Kerboul angle; the Harris hip score was used to assess clinical outcome; and conversion to THA, reoperation, and survivorship free from femoral head collapse were analyzed with the Kaplan-Meier method on a per-hip basis. RESULTS Survivorship free from THA, any procedure, and femoral head collapse was 84% (95% confidence interval [CI], 75%-93%), 67% (95% CI, 55%-79%), and 93% (95% CI, 76%-98%), respectively, at 3 years postoperatively; two patients (four hips) underwent a second decompression and MSC injection for persistent pain without signs of radiographic collapse. All patients with collapse underwent THA. The mean modified Kerboul angle improved from 205° ± 47° to 172° ± 48° postoperatively (mean change -30° ± 6°, p = 0.01). A greater proportion of patients who underwent an additional procedure had a modified Kerboul grade of 3 or 4 preoperatively (80% [four of five] versus 13% [four of 30 Grade 1 or 2; odds ratio, 26; 95% CI, 2-296; p = 0.005). Preoperatively the mean Harris hip score was 57 ± 12, which improved to 85 ± 15 (mean change 28 ± 3, p < 0.001) at most recent followup. Patients undergoing a reoperation or THA had a lower mean concentration of nucleated cells/mL (5.5 x 10 ± 2.8 x 10 cells/mL versus 2.3 x 10 ± 2.2 x 10 cells/mL, p = 0.02) and lower mean CFUs (13 ± 6 versus 19 ± 7, p = 0.04) compared with those who did not. CONCLUSIONS Core hip decompression with injection of concentrated bone marrow plus PRP improved pain and function; > 90% of hips in this series were without collapse at a minimum of 2 years. In this preliminary study, successful results were seen when nucleated cell count was high and modified Kerboul grade was low. Further randomized studies are needed to determine this procedure's efficacy versus core decompression or nonoperative treatment alone. LEVEL OF EVIDENCE Level II, therapeutic study.
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Affiliation(s)
- Matthew T Houdek
- M. T. Houdek, C. C. Wyles, R. J. Sierra, Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA M. S. Collins, B. M. Howe, Department of Radiology, Mayo Clinic, Rochester, MN, USA A. Terzic, A. Behfar, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
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27
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Kim SJ, Kim EK, Kim SJ, Song DH. Effects of bone marrow aspirate concentrate and platelet-rich plasma on patients with partial tear of the rotator cuff tendon. J Orthop Surg Res 2018; 13:1. [PMID: 29298726 PMCID: PMC5753487 DOI: 10.1186/s13018-017-0693-x] [Citation(s) in RCA: 148] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 11/24/2017] [Indexed: 11/12/2022] Open
Abstract
Background We compared the clinical course of rotator cuff tears between rotator cuff exercise and bone marrow aspirate concentration (BMAC)-platelet rich plasma (PRP) injection to identify the therapeutic effects of BMAC-PRP on partial tear of the rotator cuff tendon. Methods Twenty-four patients with partial tear of the rotator cuff tendon participated in this study. Twelve patients underwent extraction of BMACs and PRP and received the injection of BMAC-PRP at the tear site under ultrasound guidance. Twelve patients in the control group were asked to perform the rotator cuff exercise for 3 months. Visual analog scale (VAS) and manual muscle test (MMT) scores of the supraspinatus muscle were measured, and the American Shoulder and Elbow Surgeons (ASES) score was recorded before, 3 weeks, and 3 months after injection. Tear size was measured by the greatest longitudinal tear length. Results The change in the VAS differed between groups at 3 months (P = 0.039) but not at 3 weeks (P = 0.147). The ASES scores in the BMAC-PRP group changed from 39.4 ± 13.0 to 54.5 ± 11.5 at 3 weeks and 74.1 ± 8.5 at 3 months while those in the control group changed from 45.9 ± 12.4 to 56.3 ± 12.3 at 3 weeks (P = 0.712) and 62.2 ± 12.2 at 3 months (P = 0.011). The tear size decreased at 3 weeks or 3 months after the BMAC-PRP injection but was not significantly different from that in the control group. Conclusions BMAC-PRP improved pain and shoulder function in patients with partial tear of the rotator cuff tendon. Trial registration The patients were registered in the institutional board registry of Samsung Medical Center (registry number 2014-07-173). Electronic supplementary material The online version of this article (10.1186/s13018-017-0693-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sang Jun Kim
- Department of Physical and Rehabilitation Medicine, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Gangnamgu, Irwonro, 81th street, Seoul, 135-710, South Korea.
| | - Eun Kyung Kim
- Department of Physical and Rehabilitation Medicine, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Gangnamgu, Irwonro, 81th street, Seoul, 135-710, South Korea
| | - Sun Jeong Kim
- Department of Physical and Rehabilitation Medicine, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Gangnamgu, Irwonro, 81th street, Seoul, 135-710, South Korea
| | - Da Hyun Song
- Department of Physical and Rehabilitation Medicine, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Gangnamgu, Irwonro, 81th street, Seoul, 135-710, South Korea
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28
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Tao SC, Guo SC, Zhang CQ. Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach. Int J Biol Sci 2017; 13:828-834. [PMID: 28808416 PMCID: PMC5555101 DOI: 10.7150/ijbs.19776] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 04/30/2017] [Indexed: 02/07/2023] Open
Abstract
Extracellular vesicles (EVs) are a newly-discovered way by which cells communicate with their neighbors, as well as transporting cargos which once were considered to be limited by membrane barriers, including membrane proteins, cytosolic proteins and RNA. The discovery of platelet-derived EVs (P-EVs), the most abundant EVs in human blood, has been a very tortuous process. At first, P-EVs were identified as nothing but 'platelet dust', and subsequent research did not progress smoothly because of the limited research techniques to study EVs. Following leaps and bounds of technical progress in studying EVs, more and more attractive features of P-EVs were revealed and they began to be further researched. The aim of this review is to present the latest knowledge about the role of P-EVs in tissue repair and tumor progression. The potential mechanism of P-EVs is emphasized. Then the limitations of the present study and future research directions are discussed.
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Affiliation(s)
- Shi-Cong Tao
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Shang-Chun Guo
- Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Chang-Qing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
- Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
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29
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Kim SJ, Song DH, Park JW, Park S, Kim SJ. Effect of Bone Marrow Aspirate Concentrate-Platelet-Rich Plasma on Tendon-Derived Stem Cells and Rotator Cuff Tendon Tear. Cell Transplant 2017; 26:867-878. [PMID: 28105983 PMCID: PMC5657720 DOI: 10.3727/096368917x694705] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2016] [Accepted: 02/01/2017] [Indexed: 02/07/2023] Open
Abstract
Bone marrow aspirate concentrates (BMACs) and platelet-rich plasma (PRP) are good sources to control the differentiation of tendon-derived stem cells (TDSCs), but there has been no study about the effect of the BMAC-PRP complex on TDSCs and tendinopathy. The aim of this study was to investigate the effect of BMAC-PRP on the TDSCs and to find the therapeutic effect of BMAC-PRP on the rotator cuff tendon tear. The chondrogenic and osteogenic potential of TDSCs decreased, but the adipogenic potential of TDSCs revealed no significant difference when they were cocultured with BMAC-PRP. Cell proliferation was significantly greater in TDSCs cocultured with BMAC-PRP than in TDSCs. The degree of wound closure (percentage) was different between TDSCs and TDSCs with BMAC-PRP. There was no significant difference in expression of collagen type I and type III in immunocytochemical staining in the presence of BMAC-PRP. Initial visual analog scale (VAS) score was 5.8 ± 1.9, which changed to 5.0 ± 2.3 at 3 weeks and 2.8 ± 2.3 at 3 months after the BMAC-PRP injection (p < 0.01). The American Shoulder Elbow Surgeon score changed from 39.4 ± 13.0 at baseline to 52.9 ± 22.9 at 3 weeks and 71.8 ± 19.7 at 3 months after the injection (p < 0.01). The initial torn area of the rotator cuff tendon was 30.2 ± 24.5 mm2, and this area was reduced to 22.5 ± 18.9 mm2 at 3 months, but the change was not significant (p > 0.05). The data indicate that BMAC-PRP enhances the proliferation and migration of TDSCs and prevents the aberrant chondrogenic and osteogenic differentiation of TDSCs, which might provide a mechanistic basis for the therapeutic benefits of BMAC-PRP for rotator cuff tendon tear.
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Affiliation(s)
- Sun Jeong Kim
- Department of Physical and Rehabilitation Medicine, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Da Hyun Song
- Department of Physical and Rehabilitation Medicine, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jong Wook Park
- Department of Physical and Rehabilitation Medicine, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Silvia Park
- Department of Internal Medicine, Division of Hemato-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sang Jun Kim
- Department of Physical and Rehabilitation Medicine, Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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30
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Imam MA, Mahmoud SS, Holton J, Abouelmaati D, Elsherbini Y, Snow M. A systematic review of the concept and clinical applications of Bone Marrow Aspirate Concentrate in Orthopaedics. SICOT J 2017; 3:17. [PMID: 29792397 PMCID: PMC5966837 DOI: 10.1051/sicotj/2017007] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2016] [Accepted: 01/08/2017] [Indexed: 02/06/2023] Open
Abstract
INTRODUCTION Mesenchymal stem cells (MSC's) are believed to have multipotent plasticity with the capability to differentiate along multiple cell lineages such as cartilage, bone, tendon, muscle, and nerve. Such multipotency has the potential to play an important role in the repair and reconstruction of multiple tissues across a number of orthopaedic specialties. Bone marrow and fat are the most abundant and accessible source of MSC's with bone marrow aspirate the most commonly being reported to stimulate healing. METHODS This review examines the current reported 20 Q2 clinical applications of bone marrow aspirate concentrate and its effectiveness. RESULTS The published studies reported techniques of collection and preparation of BMAC in addition to its applications in a number of orthopaedic sub-specialities. Studies could be sub-categorised into: techniques of extraction, processing and microscopic examination of BMAC (31), reconstruction of osseous defects/non-union (20), treatment of avascular necrosis (9), repair of cartilage defects (8), treatment of sports injuries and tendon injury/repair (9), injection in regenerative therapy (4), treatment of spine conditions (4) including enhancing postoperative fusion and degenerative disc pathology and orthopaedic oncology (4). A few published studies combined the use of platelet-rich plasma (PRP) with BMAC (4) or compared them in different applications (5). CONCLUSIONS BMAC has been used in bone, cartilage and tendon injuries with encouraging results.
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Affiliation(s)
- Mohamed A. Imam
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Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University 41111
Ismailia Egypt
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The Royal Orthopaedic Hospital B31 2AP
Birmingham UK
| | | | - James Holton
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Department of Trauma and Orthopaedics, Faculty of Medicine, Suez Canal University 41111
Ismailia Egypt
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The Royal Orthopaedic Hospital B31 2AP
Birmingham UK
| | | | - Yasser Elsherbini
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Research and Development, OxCell OX3 8AT
Oxford UK
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Institute of Biomedical Engineering, University of Oxford OX3 7DQ
Oxford UK
| | - Martyn Snow
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The Royal Orthopaedic Hospital B31 2AP
Birmingham UK
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Birmingham University B15 2TT
Birmingham UK
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31
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Kraeutler MJ, Garabekyan T, Mei-Dan O. The use of platelet-rich plasma to augment conservative and surgical treatment of hip and pelvic disorders. Muscles Ligaments Tendons J 2016; 6:410-419. [PMID: 28066748 DOI: 10.11138/mltj/2016.6.3.410] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND In recent years, platelet-rich plasma (PRP) has gained popularity within the orthopaedic community as a treatment modality to enhance tissue healing. PURPOSE This review aims to concisely present the current indications for PRP injections in the treatment of hip and pelvic pathologies and to describe some novel applications for PRP which have not yet been reported in the literature. METHODS We reviewed the literature on the non-operative and operative indications for PRP in the treatment of hip and pelvic pathologies. CONCLUSIONS With regard to hip and pelvic pathologies, PRP injections are used most commonly as a non-operative intervention, and have been described in the literature to treat osteoarthritis of the hip joint as well as tendinopathy of the hamstrings, adductor longus, and gluteus medius. In contrast, most of the surgical applications of PRP for the hip are novel, with few reported studies in the literature. Because of the increasing awareness of PRP's beneficial effects on musculoskeletal healing and thus the growing number of indications for its use, this review also describes some novel applications for PRP, including osteitis pubis, post-microfracture of the hip, tears of the rectus femoris, and avulsion of the sartorius muscle. LEVEL OF EVIDENCE V.
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Affiliation(s)
- Matthew J Kraeutler
- University of Colorado School of Medicine, Department of Orthopedics, Aurora, USA
| | | | - Omer Mei-Dan
- Hip Preservation/Sports Medicine/Orthopedics University of Colorado
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32
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Yin H, Yuan Z, Wang D. Multiple drilling combined with simvastatin versus multiple drilling alone for the treatment of avascular osteonecrosis of the femoral head: 3-year follow-up study. BMC Musculoskelet Disord 2016; 17:344. [PMID: 27528281 PMCID: PMC4986261 DOI: 10.1186/s12891-016-1199-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2016] [Accepted: 08/03/2016] [Indexed: 12/15/2022] Open
Abstract
Background Multiple small drilling for core decompression is widely used to preserve the femoral head in patients with avascular necrosis of the femoral head (ANFH). Nevertheless, the clinical outcome remains controversial. Simvastatin has been demonstrated to promote bone formation and reduce bone adsorption. The purpose of this study was to determine whether simvastatin enhanced the effect of multiple decompressions in preventing progression of ANFH and to identify independent risk factors associated with poor results. Methods We retrospectively analyzed 58 hips in 36 patients, with a follow-up of 36 months. 20 patients (32 hips) underwent multiple drilling combined with simvastatin treatment (SIM group); 16 patients (26 hips) underwent multiple drilling alone (MD group). We defined clinical failure as a requirement for subsequent hip surgery or Harris Hip Score < 75. New occurrence of collapse or increased collapse > 2 mm on plain radiographs was defined as radiological failure. Results Successful clinical results were achieved in 27 of 32 hips (84 %) in the SIM group compared with 15 of 26 hips (58 %) in the MD group (OR = 0.2, CI (0.1, 0.6.), P = 0.032). Successful radiological results were achieved in 27 of 32 hips (84 %) in the SIM group and in 16 of 26 hips (61.5 %) in the MD group (P = 0.048). Body mass index, disease stage and location of lesion were independent prognostic factors for overall survival. Conclusions We believe that simvastatin could enhance the effects of multiple decompressions in preventing progression of ANFH and reducing the risk of femoral head collapse.
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Affiliation(s)
- Han Yin
- Department of Orthopaedics, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, No. 67, Dongchang Road, Liaocheng, Shandong, China
| | - Zhenfeng Yuan
- Department of Orthopaedics, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, No. 67, Dongchang Road, Liaocheng, Shandong, China.
| | - Dawei Wang
- Department of Orthopaedics, Liaocheng People's Hospital and Liaocheng Clinical School of Taishan Medical University, No. 67, Dongchang Road, Liaocheng, Shandong, China
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33
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Arbeloa-Gutierrez L, Dean CS, Chahla J, Pascual-Garrido C. Core Decompression Augmented With Autologous Bone Marrow Aspiration Concentrate for Early Avascular Necrosis of the Femoral Head. Arthrosc Tech 2016; 5:e615-20. [PMID: 27656386 PMCID: PMC5021452 DOI: 10.1016/j.eats.2016.02.009] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 02/04/2016] [Indexed: 02/03/2023] Open
Abstract
Lack of necessary perfusion to the femoral head can lead to necrosis of the underlying bone (avascular necrosis) and result in femoral and acetabular surface changes in advanced stages. Numerous treatments have been reported in the literature, including nonoperative and surgical procedures. In addition to the standard core decompression, we describe the use of bone marrow aspirate to stimulate a healing response and bone grafting, allowing for immediate weight bearing postoperatively. The purpose of this article was to describe our method of core decompression augmented with bone marrow aspirate concentrate and bone grafting for the treatment of early avascular necrosis of the femoral head.
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Affiliation(s)
| | - Chase S. Dean
- Steadman Philippon Research Institute, Vail, Colorado, U.S.A
| | - Jorge Chahla
- Steadman Philippon Research Institute, Vail, Colorado, U.S.A
| | - Cecilia Pascual-Garrido
- Department of Orthopedics, University of Colorado, Aurora, Colorado, U.S.A.,Address correspondence to Cecilia Pascual-Garrido, M.D., Department of Orthopedics, University of Colorado, University of Colorado Hospital, Anschutz Outpatient Pavilion, 1635 N Aurora Ct, Aurora, CO 80045, U.S.A.Department of OrthopedicsUniversity of ColoradoUniversity of Colorado HospitalAnschutz Outpatient Pavilion1635 N Aurora CtAuroraCO80045U.S.A.
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34
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Houdek MT, Wyles CC, Packard BD, Terzic A, Behfar A, Sierra RJ. Decreased Osteogenic Activity of Mesenchymal Stem Cells in Patients With Corticosteroid-Induced Osteonecrosis of the Femoral Head. J Arthroplasty 2016; 31:893-8. [PMID: 26404846 DOI: 10.1016/j.arth.2015.08.017] [Citation(s) in RCA: 86] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Revised: 08/18/2015] [Accepted: 08/26/2015] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Osteonecrosis (ON) of the femoral head occurs when cells of trabecular bone spontaneously die. Mesenchymal stem cells (MSCs) have been introduced into the femoral head in an attempt to halt progression of the disease. The purpose of this study was to functionally compare MSCs in patients with ON of the femoral head with patients without. METHODS Mesenchymal stem cells were isolated from 20 patients with corticosteroid-induced ON and 10 controls without. Colony-forming unit and proliferation assays were used to assess MSC proliferation. Mesenchymal stem cells were differentiated into bone, fat, and cartilage. Functional assays were used to quantify the differentiation capacity. RESULTS Control MSCs demonstrated greater cellular growth potential and improved ability to differentiate into bone. CONCLUSION The decreased ability to differentiate into bone may be a reason why patients treated with autologous MSC infusion fail regenerative treatment strategies and progress to collapse.
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Affiliation(s)
- Matthew T Houdek
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Cody C Wyles
- Mayo Medical School, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Andre Terzic
- Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Atta Behfar
- Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Rafael J Sierra
- Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
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35
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Mont MA, Cherian JJ, Sierra RJ, Jones LC, Lieberman JR. Nontraumatic Osteonecrosis of the Femoral Head: Where Do We Stand Today? A Ten-Year Update. J Bone Joint Surg Am 2015; 97:1604-27. [PMID: 26446969 DOI: 10.2106/jbjs.o.00071] [Citation(s) in RCA: 331] [Impact Index Per Article: 33.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
➤ Although multiple theories have been proposed, no one pathophysiologic mechanism has been identified as the etiology for the development of osteonecrosis of the femoral head. However, the basic mechanism involves impaired circulation to a specific area that ultimately becomes necrotic.➤ A variety of nonoperative treatment regimens have been evaluated for the treatment of precollapse disease, with varying success. Prospective, multicenter, randomized trials are needed to evaluate the efficacy of these regimens in altering the natural history of the disease.➤ Joint-preserving procedures are indicated in the treatment of precollapse disease, with several studies showing successful outcomes at mid-term and long-term follow-up.➤ Studies of total joint arthroplasty, once femoral head collapse is present, have described excellent outcomes at greater than ten years of follow-up, which is a major advance and has led to a paradigm shift in treating these patients.➤ The results of hemiresurfacing and total resurfacing arthroplasty have been suboptimal, and these procedures have restricted indications in patients with osteonecrosis of the femoral head.
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Affiliation(s)
- Michael A Mont
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215. E-mail address for M.A. Mont:
| | - Jeffrey J Cherian
- Rubin Institute for Advanced Orthopedics, Center for Joint Preservation and Replacement, Sinai Hospital of Baltimore, 2401 West Belvedere Avenue, Baltimore, MD 21215. E-mail address for M.A. Mont:
| | - Rafael J Sierra
- Mayo Clinic, 200 First Street S.W., Gonda 14 South, Rochester, MN 55905
| | - Lynne C Jones
- Department of Orthopaedic Surgery, Johns Hopkins University, 601 North Caroline Street, JHOC 5245, Baltimore, MD 21287
| | - Jay R Lieberman
- Keck Medical Center of University of Southern California, 1520 San Pablo Street, Suite 2000, Los Angeles, CA 90033
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Adipose-derived Mesenchymal Stem Cells Are Phenotypically Superior for Regeneration in the Setting of Osteonecrosis of the Femoral Head. Clin Orthop Relat Res 2015; 473:3080-90. [PMID: 26070774 PMCID: PMC4562944 DOI: 10.1007/s11999-015-4385-8] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 05/29/2015] [Indexed: 01/31/2023]
Abstract
BACKGROUND Bone marrow-derived mesenchymal stem cells (bmMSCs) have been used as a cellular therapeutic option for treatment of osteonecrosis of the femoral head. However, use of bmMSCs as a treatment adjuvant for orthopaedic disorders in general has achieved limited success. Adipose-derived MSCs (aMSCs) may be a more-efficient regenerative cell source given their greater quantity and protection from physiologic stress. QUESTIONS/PURPOSES We asked the following questions in a paired analysis of MSCs from patients with osteonecrosis: (1) Is there a difference in proliferation potential between aMSCs and bmMSCs? (2) Is there a difference in osteogenic differentiation potential between aMSCs and bmMSCs? (3) Are genetic pathways differentially expressed between aMSCs and bmMSCs that may govern functional phenotypic discrepancies? METHODS Periarticular samples of adipose tissue and bone marrow from the femoral canal were obtained from 15 patients undergoing hip replacement for late-stage (Steinberg Stages III-VI) osteonecrosis. MSCs were isolated from both tissue sources and taken through a standardized 20-day cell division protocol to establish cumulative cell count. They also were grown in osteogenic differentiation media for 14 days with subsequent measurement of alkaline phosphatase in units of optical density. RNA was isolated from aMSCs and bmMSCs in five patients to assess differentially expressed genetic pathways using the Affymetrix GeneChip Human Transcriptome Array 2.0 platform. RESULTS Proliferation capacity was increased by fourfold in aMSCs compared with bmMSCs after 20 days in culture. The mean difference in cumulative cell count was 3.99 × 10(8) cells (SD = 1.67 × 10(8) cells; 95% CI, 3.07 × 10(8)-4.92 × 10(8) cells; p < 0.001). Bone differentiation efficiency as measured by optical density was increased by 2.25-fold in aMSCs compared with bmMSCs. The mean difference in optical density was 1.27 (SD = 0.34; 95% CI, 1.08-1.46; p < 0.001). RNA transcriptome analysis showed 284 genes that met statistical (p < 0.05) and biological (fold change > 1.5) significance cutoffs for differential expression between cell populations. Subsequent network topology of differentially expressed genes showed alterations in pathways critical for musculoskeletal tissue development in addition to many nonspecific findings. CONCLUSIONS aMSCs outperform bmMSCs in growth rate and bone differentiation potential in the setting of osteonecrosis, suggesting they may provide a more-potent regenerative therapeutic strategy in this population. Differential expression of genes and cellular pathways highlighted in this study may provide therapeutic targets for cellular optimization or acellular treatment strategies. CLINICAL RELEVANCE aMSCs may provide a more robust cellular therapeutic than bmMSCs for treatment of osteonecrosis. Ideally, a well-designed prospective study will be able to evaluate the efficacy of these cellular therapies side-by-side in patients with bilateral early stage disease.
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Houdek MT, Wyles CC, Sierra RJ. Osteonecrosis of the femoral head: treatment with ancillary growth factors. Curr Rev Musculoskelet Med 2015; 8:233-9. [PMID: 25985987 PMCID: PMC4596200 DOI: 10.1007/s12178-015-9281-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Osteonecrosis (ON) of the femoral head, also known as avascular necrosis (AVN) of the femoral head, is a progressive disease that predominantly affects younger patients. During early stage of ON, decompression of the femoral head has been commonly used to improve pain. The decompression has been augmented with nonvascularized or vascularized bone grafts, mesenchymal stems cells, and growth factors. The use of adjuvant growth factors to supplement the core decompression has mainly been limited to animal models in an attempt to regenerate the necrotic lesion of ON. Factors utilized include bone morphogenetic proteins, vascular endothelial growth factors, hepatocyte growth factors, fibroblast growth factors, granulocyte colony-stimulating factors, and stem cells factors. In animal models, the use of these factors has been shown to increase bone formation and angiogenesis. Although promising, the use of these growth factors and cell-based therapies clinically remains limited.
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Affiliation(s)
- Matthew T. Houdek
- />Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 USA
| | - Cody C. Wyles
- />Mayo Clinic Medical School, 200 First St. SW, Rochester, MN 55909 USA
| | - Rafael J. Sierra
- />Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 USA
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Alshameeri Z, McCaskie A. The role of orthobiologics in hip preservation surgery. J Hip Preserv Surg 2015; 2:339-54. [PMID: 27011858 PMCID: PMC4732367 DOI: 10.1093/jhps/hnv042] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2015] [Revised: 04/21/2015] [Accepted: 05/17/2015] [Indexed: 02/06/2023] Open
Abstract
The potential regenerative role of different orthobiologics is becoming more recognized for the treatment of chronic and degenerative musculoskeletal conditions. Over the last few years there has been an increasing number of publications on cell therapy and other orthobiologics for the treatment of avascular necrosis of the femoral head and other hip conditions with promising short–term clinical results. In this article, we have used a systematic search of the literature to identify potentially relevant topics on orthobiologics and then selected those most applicable to hip preservation surgery. We identified several innovative strategies and present a summary of the currently available evidence on their potential role in hip preservation surgery. For many of these treatment strategies there was a lack of clinical evidence and therefore we suggest that there is a need for comparative studies in this field.
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Affiliation(s)
- Zeiad Alshameeri
- 1. Health Education East of England, 2-4 victoria house, Cambridge, CB21 5XB
| | - Andrew McCaskie
- 2. Division of Trauma and Orthopaedic Surgery, Department of Surgery, University of Cambridge and; 3. Arthritis Research UK Tissue Engineering Centre
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Rehabilitation program after mesenchymal stromal cell transplantation augmented by vascularized bone grafts for idiopathic osteonecrosis of the femoral head: a preliminary study. Arch Phys Med Rehabil 2014; 96:532-9. [PMID: 25450129 DOI: 10.1016/j.apmr.2014.09.040] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2014] [Revised: 09/23/2014] [Accepted: 09/30/2014] [Indexed: 01/24/2023]
Abstract
OBJECTIVE To determine the feasibility and safety of implementing a 12-week rehabilitation program after mesenchymal stromal cell (MSC) transplantation augmented by vascularized bone grafting for idiopathic osteonecrosis (ION) of the femoral head. DESIGN A prospective case series. SETTING University clinical research laboratory. PARTICIPANTS Participants (N=10) with ION who received MSC transplantation augmented by vascularized bone grafting. INTERVENTION A 12-week exercise program, which included range-of-motion (ROM) exercises, muscle-strengthening exercises, and aerobic training. MAIN OUTCOME MEASURES Measures of ROM, muscle strength, Timed Up and Go test, and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) were collected before surgery and again at 6 and 12 months after surgery. RESULTS All participants completed the 12-week program. External rotation ROM as well as extensor and abductor muscle strength significantly improved 6 months after treatment compared with that before treatment (P<.05). Significant improvements were also seen in physical function, role physical, and bodily pain subgroup scores of the SF-36 (P<.05). No serious adverse events occurred. CONCLUSIONS This study demonstrates the feasibility and safety of a multiplex rehabilitation program after MSC transplantation and provides support for further study on the benefits of rehabilitation programs in regenerative medicine.
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Houdek MT, Wyles CC, Martin JR, Sierra RJ. Stem cell treatment for avascular necrosis of the femoral head: current perspectives. STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS 2014; 7:65-70. [PMID: 24744611 PMCID: PMC3986287 DOI: 10.2147/sccaa.s36584] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Avascular necrosis (AVN) of the femoral head is a progressive disease that predominantly affects younger patients. Although the exact pathophysiology of AVN has yet to be elucidated, the disease is characterized by a vascular insult to the blood supply of the femoral head, which can lead to collapse of the femoral head and subsequent degenerative changes. If AVN is diagnosed in the early stages of the disease, it may be possible to attempt surgical procedures which preserve the hip joint, including decompression of the femoral head augmented with concentrated bone marrow. The use of autologous stem cells has shown promise in halting the progression of AVN of the femoral head, and subsequently preventing young patients from undergoing total hip arthroplasty. The purpose of this study was to review the current use of stem cells for the treatment of AVN of the femoral head.
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Affiliation(s)
| | - Cody C Wyles
- School of Medicine, Mayo Clinic, Rochester, MN, USA
| | - John R Martin
- Department of Orthopedic Surgery, Rochester, MN, USA
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Terzic A, Harper CM, Gores GJ, Pfenning MA. Regenerative Medicine Blueprint. Stem Cells Dev 2013; 22 Suppl 1:20-4. [DOI: 10.1089/scd.2013.0448] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Affiliation(s)
- Andre Terzic
- Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
| | - C. Michel Harper
- Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
| | - Gregory J. Gores
- Center for Regenerative Medicine, Mayo Clinic, Rochester, Minnesota
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