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Lanci A, Iacono E, Merlo B. Therapeutic Application of Extracellular Vesicles Derived from Mesenchymal Stem Cells in Domestic Animals. Animals (Basel) 2024; 14:2147. [PMID: 39123673 PMCID: PMC11310970 DOI: 10.3390/ani14152147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 07/12/2024] [Accepted: 07/20/2024] [Indexed: 08/12/2024] Open
Abstract
Recently, the therapeutic potential of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) has been extensively studied in both human and veterinary medicine. EVs are nano-sized particles containing biological components commonly found in other biological materials. For that reason, EV isolation and characterization are critical to draw precise conclusions during their investigation. Research on EVs within veterinary medicine is still considered in its early phases, yet numerous papers were published in recent years. The conventional adult tissues for deriving MSCs include adipose tissue and bone marrow. Nonetheless, alternative sources such as synovial fluid, endometrium, gingiva, and milk have also been intermittently used. Fetal adnexa are amniotic membrane/fluid, umbilical cord and Wharton's jelly. Cells derived from fetal adnexa exhibit an intermediate state between embryonic and adult cells, demonstrating higher proliferative and differentiative potential and longer telomeres compared to cells from adult tissues. Summarized here are the principal and recent preclinical and clinical studies performed in domestic animals such as horse, cattle, dog and cat. To minimize the use of antibiotics and address the serious issue of antibiotic resistance as a public health concern, they will undoubtedly also be utilized in the future to treat infections in domestic animals. A number of concerns, including large-scale production with standardization of EV separation and characterization techniques, must be resolved for clinical application.
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Affiliation(s)
- Aliai Lanci
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sora 50, Ozzano dell’Emilia, 40064 Bologna, Italy; (E.I.); (B.M.)
| | - Eleonora Iacono
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sora 50, Ozzano dell’Emilia, 40064 Bologna, Italy; (E.I.); (B.M.)
- Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40100 Bologna, Italy
| | - Barbara Merlo
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sora 50, Ozzano dell’Emilia, 40064 Bologna, Italy; (E.I.); (B.M.)
- Health Science and Technologies Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, 40100 Bologna, Italy
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Barrère-Lemaire S, Vincent A, Jorgensen C, Piot C, Nargeot J, Djouad F. Mesenchymal stromal cells for improvement of cardiac function following acute myocardial infarction: a matter of timing. Physiol Rev 2024; 104:659-725. [PMID: 37589393 DOI: 10.1152/physrev.00009.2023] [Citation(s) in RCA: 31] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 07/05/2023] [Accepted: 08/16/2023] [Indexed: 08/18/2023] Open
Abstract
Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.
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Affiliation(s)
- Stéphanie Barrère-Lemaire
- Institut de Génomique Fonctionnelle, Université de Montpellier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- LabEx Ion Channel Science and Therapeutics, Université de Nice, Nice, France
| | - Anne Vincent
- Institut de Génomique Fonctionnelle, Université de Montpellier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- LabEx Ion Channel Science and Therapeutics, Université de Nice, Nice, France
| | - Christian Jorgensen
- Institute of Regenerative Medicine and Biotherapies, Université de Montpellier, Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- Centre Hospitalier Universitaire Montpellier, Montpellier, France
| | - Christophe Piot
- Département de Cardiologie Interventionnelle, Clinique du Millénaire, Montpellier, France
| | - Joël Nargeot
- Institut de Génomique Fonctionnelle, Université de Montpellier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- LabEx Ion Channel Science and Therapeutics, Université de Nice, Nice, France
| | - Farida Djouad
- Institute of Regenerative Medicine and Biotherapies, Université de Montpellier, Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- Centre Hospitalier Universitaire Montpellier, Montpellier, France
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Intra-Articular Injection of Autologous Micro-Fragmented Adipose Tissue for the Treatment of Knee Osteoarthritis: A Prospective Interventional Study. J Pers Med 2023; 13:jpm13030504. [PMID: 36983686 PMCID: PMC10059754 DOI: 10.3390/jpm13030504] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/03/2023] [Accepted: 03/04/2023] [Indexed: 03/14/2023] Open
Abstract
Background: To investigate the efficacy and safety of autologous micro-fragmented adipose tissue (MF-AT) for improving joint function and cartilage repair in patients with knee osteoarthritis. Methods: From March 2019 to December 2020, 20 subjects (40 knees) between 50 and 65 years old suffering from knee osteoarthritis were enrolled in the study and administered a single injection of autologous MF-A. The data of all patients were prospectively collected. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), knee society score (KSS), hospital for special surgery (HSS) score, visual analogue score (VAS) pain score, changes in cartilage Recht grade on magnetic resonance imaging (MRI) and adverse events were analyzed before and 3, 6, 9, 12 and 18 months after injection. Results: The WOMAC, VAS, KSS and HSS scores at 3, 6, 9, 12 and 18 months after injection were improved compared with those before injection (p < 0.05). There was no significant difference in WOMAC scores between 9 and 12 months after injection (p > 0.05), but the WOMAC score 18 months after injection was worse than that at the last follow-up (p < 0.05). The VAS, KSS and HSS scores 9, 12 and 18 months after injection were worse than those at the last follow-up (p < 0.05). The Recht score improvement rate was 25%. No adverse events occurred during the follow-up. Conclusions: Autologous MF-AT improves knee function and relieves pain with no adverse events. However, the improved knee function was not sustained, with the best results occurring 9–12 months after injection and the cartilage regeneration remaining to be investigated.
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Khasru MR, Siddiq MAB, Jubery TAZN, Marzen T, Hoque A, Ahmed AZ, Begum M, Chowdhury FR, Salek AKM, Khan MM. Outcome of Intra-articular Injection of Total Stromal Cells and Platelet-Rich Plasma in Primary Knee Osteoarthritis: A Randomized Clinical Trial. Cureus 2023; 15:e34595. [PMID: 36883080 PMCID: PMC9985905 DOI: 10.7759/cureus.34595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/03/2023] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Mesenchymal stem cell (MSC) therapy appeared promising in knee osteoarthritis (OA). We examined if a single intra-articular (IA) autologous total stromal cells (TSC) and platelet-rich plasma (PRP) injection improved knee pain, physical function, and articular cartilage thickness in knee OA. METHODS The study was performed in the physical medicine and rehabilitation department of Bangabandhu Shaikh Mujib Medical University, Dhaka, Bangladesh. Knee OA was diagnosed according to the American College of Rheumatology criteria and randomly assigned to treatment (received TSC and PRP) and control groups. Kallgreen-Lawrance (KL) scoring system was used to grade primary knee OA. The Visual Analogue Scale (VAS, 0-10 cm) for pain, WOMAC (Western Ontario and McMaster Universities Arthritis Index) for physical function, and medial femoral condylar cartilage (MFC) thickness (millimeters) under ultrasonogram (US) were documented and compared between groups before and after treatment. Statistical Package analyzed data for Social Scientists (SPSS 22.0; IBM Corp, Armonk, NY) was used for data analysis. Pre- and post-intervention outcomes were measured using the Wilcoxon-sign test, whereas Mann-Whitney U-test calculated the difference between groups; a p-value <0.05 was considered statistically significant. Result: In the treatment group, 15 received IA-TSC and PRP preparation, and in the control group, 15 patients received no injection, but quadricep muscle-strengthening exercise. There was no significant difference between groups regarding VAS for pain, WOMAC physical function, and cartilage thickness before starting the treatment and two weeks after intervention. VAS for pain and WOMAC physical function scores improved profoundly in the treatment group after 12 and 24 weeks of intervention; the pain and physical function scores difference between groups was also significant. However, significant mean femoral cartilage thickness was not changed until the end of 24 weeks (U=175.00, p=0.009 two-tailed and U= 130.00, p=0.016 two-tailed, respectively, for right and left knee). CONCLUSION Single TSC and PRP injection reduces knee pain and improves physical function and cartilage thickness in knee OA. While pain and physical function improvement happen earlier, cartilage thickness change takes more time.
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Affiliation(s)
- Moshiur R Khasru
- Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Md Abu B Siddiq
- Physical Medicine and Rehabilitation, Brahmanbaria Medical College, Brahmanbaria, BGD.,Rheumatology, University of South Wales, Pontypridd, Wales, GBR
| | | | - Tangila Marzen
- Anatomy, Shaheed Suhrawardy Medical College Hospital, Dhaka, BGD
| | - Ashraful Hoque
- Blood Transfusion, Sheikh Hasina National Institute of Burn & Plastic Surgery, Dhaka, BGD
| | - Akm Zahir Ahmed
- Musculoskeletal Sonography, Module General Hospital, Dhaka, BGD
| | - Masuda Begum
- Hematology, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Fazle R Chowdhury
- Internal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Abul Khair M Salek
- Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
| | - Md Moniruzzaman Khan
- Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University, Dhaka, BGD
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Goswami AG, Basu S, Huda F, Pant J, Ghosh Kar A, Banerjee T, Shukla VK. An appraisal of vascular endothelial growth factor (VEGF): the dynamic molecule of wound healing and its current clinical applications. Growth Factors 2022; 40:73-88. [PMID: 35584274 DOI: 10.1080/08977194.2022.2074843] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Angiogenesis is a critical step of wound healing, and its failure leads to chronic wounds. The idea of restoring blood flow to the damaged tissues by promoting neo-angiogenesis is lucrative and has been researched extensively. Vascular endothelial growth factor (VEGF), a key dynamic molecule of angiogenesis has been investigated for its functions. In this review, we aim to appraise its biology, the comprehensive role of this dynamic molecule in the wound healing process, and how this knowledge has been translated in clinical application in various types of wounds. Although, most laboratory research on the use of VEGF is promising, its clinical applications have not met great expectations. We discuss various lacunae that might exist in making its clinical application unsuccessful for commercial use, and provide insight to the foundation for future research.
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Affiliation(s)
- Aakansha Giri Goswami
- Department of General surgery, All India Institute of Medical Sciences, Rishikesh, India
| | - Somprakas Basu
- Department of General surgery, All India Institute of Medical Sciences, Rishikesh, India
| | - Farhanul Huda
- Department of General surgery, All India Institute of Medical Sciences, Rishikesh, India
| | - Jayanti Pant
- Department of Physiology, All India Institute of Medical Sciences, Rishikesh, India
| | - Amrita Ghosh Kar
- Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Tuhina Banerjee
- Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
| | - Vijay Kumar Shukla
- Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
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Park YM, Yang CM, Cho HY. Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model. Int J Mol Sci 2022; 23:6877. [PMID: 35805883 PMCID: PMC9266974 DOI: 10.3390/ijms23136877] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 06/17/2022] [Accepted: 06/18/2022] [Indexed: 02/01/2023] Open
Abstract
In patients with type 1 diabetes (T1D), compromised pancreatic β-cell functions are compensated through daily insulin injections or the transplantation of pancreatic tissue or islet cells. However, both approaches are associated with specific challenges. The transplantation of mesenchymal stem cells (MSCs) represents a potential alternative, as MSCs have tissue-forming capacity and can be isolated from various tissues. The human umbilical cord (hUC) is a good source of freely available MSCs, which can be collected through pain-free, non-invasive methods subject to minimal ethical concerns. We sought to develop a method for the in vitro generation of insulin-producing cells (IPCs) using MSCs. We examined the potential therapeutic uses and efficacy of IPCs generated from hUC-derived MSCs (hUC-IPCs) and human adipose tissue (hAD)-derived MSCs (hAD-IPCs) through in vitro experiments and streptozotocin (STZ)-induced C57BL/6 T1D mouse models. We discovered that compared to hAD-IPCs, hUC-IPCs exhibited a superior insulin secretion capacity. Therefore, hUC-IPCs were selected as candidates for T1D cell therapy in mice. Fasting glucose and intraperitoneal glucose tolerance test levels were lower in hUC-IPC-transplanted mice than in T1D control mice and hAD-IPC-transplanted mice. Our findings support the potential use of MSCs for the treatment of T1D.
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Affiliation(s)
- Yu Mi Park
- CHA Advanced Research Institute, 335, Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Korea
- Department of Biomedical Science, CHA University, 335, Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Korea
- Cell Therapy R&D Center, HansBiomed Corp, 7, Jeongui-ro 8-gil, Songpa-gu, Seoul 05836, Gyeonggi-do, Korea; (C.M.Y.); (H.Y.C.)
| | - Chang Mo Yang
- Cell Therapy R&D Center, HansBiomed Corp, 7, Jeongui-ro 8-gil, Songpa-gu, Seoul 05836, Gyeonggi-do, Korea; (C.M.Y.); (H.Y.C.)
| | - Hee Yeon Cho
- Cell Therapy R&D Center, HansBiomed Corp, 7, Jeongui-ro 8-gil, Songpa-gu, Seoul 05836, Gyeonggi-do, Korea; (C.M.Y.); (H.Y.C.)
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Yang YP, Lai WY, Lin TW, Lin YY, Chien Y, Tsai YC, Tai HY, Wang CL, Liu YY, Huang PI, Chen YW, Lo WL, Wang CY. Autophagy reprogramming stem cell pluripotency and multiple-lineage differentiation. J Chin Med Assoc 2022; 85:667-671. [PMID: 35385421 DOI: 10.1097/jcma.0000000000000728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
The cellular process responsible for the degradation of cytosolic proteins and subcellular organelles in lysosomes was termed "autophagy." This process occurs at a basal level in most tissues as part of tissue homeostasis that redounds to the regular turnover of components inside cytoplasm. The breakthrough in the autophagy field is the identification of key players in the autophagy pathway, compounded under the name "autophagy-related genes" (ATG) encoding for autophagy effector proteins. Generally, the function of autophagy can be classified into two divisions: intracellular clearance of defective macromolecules and organelles and generation of degradation products. Therapeutic strategies using stem cell-based approach come as a promising therapy and develop rapidly recently as stem cells have high self-renewability and differentiation capability as known as mesenchymal stem cells (MSCs). They are defined as adherent fibroblast-like population with the abilities to self-renew and multi-lineage differentiate into osteogenic, adipogenic, and chondrogenic lineage cells. To date, they are the most extensively applied adult stem cells in clinical trials. The properties of MSCs, such as immunomodulation, neuroprotection, and tissue repair pertaining to cell differentiation, processes to replace lost, or damaged cells, for aiding cell repair and revival. Autophagy has been viewed as a remarkable mechanism for maintaining homeostasis, ensuring the adequate function and survival of long-lived stem cells. In addition, authophagy also plays a remarkable role in protecting stem cells against cellular stress when the stem cell regenerative capacity is harmed in aging and cellular degeneration. Understanding the under-explored mechanisms of MSC actions and expanding the spectrum of their clinical applications may improve the utility of the MSC-based therapeutic approach in the future.
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Affiliation(s)
- Yi-Ping Yang
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Wei-Yi Lai
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Tzu-Wei Lin
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Ying Lin
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yueh Chien
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yi-Ching Tsai
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Hsiao-Yun Tai
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Chia-Lin Wang
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yung-Yang Liu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Pin-I Huang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Yi-Wei Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Wen-Liang Lo
- Institute of Oral Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Oral and Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Dentistry, School of Dentistry, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Chien-Ying Wang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Department of Critical Care Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Division of Trauma, Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Physical Education and Health, University of Taipei, Taipei, Taiwan, ROC
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Smolinska V, Debreova M, Culenova M, Csobonyeiova M, Svec A, Danisovic L. Implication of Mesenchymal Stem Cells and Their Derivates for Osteochondral Regeneration. Int J Mol Sci 2022; 23:2490. [PMID: 35269633 PMCID: PMC8910214 DOI: 10.3390/ijms23052490] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/11/2022] [Accepted: 02/15/2022] [Indexed: 02/04/2023] Open
Abstract
Healing of articular cartilage defects presents a challenging issue, due to its regenerative shortcomings. Lacking vascularity and innervation of cartilage and low proliferative potential of chondrocytes are the main reasons for the limited healing potential of articular cartilage. Traditional reparative approaches are limited in their efficiency, hence there is a demand for novel reparative treatments. Mesenchymal stromal cells, preferred for clinical uses, can be readily derived from various sources and have been proven to have a therapeutic effect on cartilage and subchondral bone. Therefore, mesenchymal stromal cells, their derivates, and scaffolds have been utilized in research targeting osteochondral regeneration. The present review aims to comprehensively outline and discuss literature considering this topic published within last 5 years.
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Affiliation(s)
- Veronika Smolinska
- Faculty of Medicine, Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia; (V.S.); (M.C.)
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia;
| | - Michaela Debreova
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia;
| | - Martina Culenova
- Faculty of Medicine, Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia; (V.S.); (M.C.)
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia;
| | - Maria Csobonyeiova
- Faculty of Medicine, Institute of Histology and Embryology, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia;
| | - Andrey Svec
- 1st Department of Orthopaedics and Traumatology, Faculty of Medicine, Comenius University, Pazitkova 4, 821 01 Bratislava, Slovakia;
| | - Lubos Danisovic
- Faculty of Medicine, Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia; (V.S.); (M.C.)
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia;
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Kulus M, Sibiak R, Stefańska K, Zdun M, Wieczorkiewicz M, Piotrowska-Kempisty H, Jaśkowski JM, Bukowska D, Ratajczak K, Zabel M, Mozdziak P, Kempisty B. Mesenchymal Stem/Stromal Cells Derived from Human and Animal Perinatal Tissues-Origins, Characteristics, Signaling Pathways, and Clinical Trials. Cells 2021; 10:cells10123278. [PMID: 34943786 PMCID: PMC8699543 DOI: 10.3390/cells10123278] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 11/13/2021] [Accepted: 11/19/2021] [Indexed: 12/15/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are currently one of the most extensively researched fields due to their promising opportunity for use in regenerative medicine. There are many sources of MSCs, of which cells of perinatal origin appear to be an invaluable pool. Compared to embryonic stem cells, they are devoid of ethical conflicts because they are derived from tissues surrounding the fetus and can be safely recovered from medical waste after delivery. Additionally, perinatal MSCs exhibit better self-renewal and differentiation properties than those derived from adult tissues. It is important to consider the anatomy of perinatal tissues and the general description of MSCs, including their isolation, differentiation, and characterization of different types of perinatal MSCs from both animals and humans (placenta, umbilical cord, amniotic fluid). Ultimately, signaling pathways are essential to consider regarding the clinical applications of MSCs. It is important to consider the origin of these cells, referring to the anatomical structure of the organs of origin, when describing the general and specific characteristics of the different types of MSCs as well as the pathways involved in differentiation.
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Affiliation(s)
- Magdalena Kulus
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
| | - Rafał Sibiak
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
- Division of Reproduction, Department of Obstetrics, Gynecology, and Gynecologic Oncology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Katarzyna Stefańska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
| | - Maciej Zdun
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
| | - Maria Wieczorkiewicz
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
| | - Hanna Piotrowska-Kempisty
- Department of Basic and Preclinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.Z.); (M.W.); (H.P.-K.)
- Department of Toxicology, Poznan University of Medical Sciences, 60-631 Poznan, Poland
| | - Jędrzej M. Jaśkowski
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (J.M.J.); (D.B.)
| | - Dorota Bukowska
- Department of Diagnostics and Clinical Sciences, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (J.M.J.); (D.B.)
| | - Kornel Ratajczak
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
| | - Maciej Zabel
- Division of Anatomy and Histology, University of Zielona Gora, 65-046 Zielona Gora, Poland;
| | - Paul Mozdziak
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA;
| | - Bartosz Kempisty
- Department of Veterinary Surgery, Institute of Veterinary Medicine, Nicolaus Copernicus University in Torun, 87-100 Torun, Poland; (M.K.); (K.R.)
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (R.S.); (K.S.)
- Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA;
- Department of Anatomy, Poznan University of Medical Sciences, 60-781 Poznan, Poland
- Correspondence:
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Park YJ, Farooq J, Cho J, Sadanandan N, Cozene B, Gonzales-Portillo B, Saft M, Borlongan MC, Borlongan MC, Shytle RD, Willing AE, Garbuzova-Davis S, Sanberg PR, Borlongan CV. Fighting the War Against COVID-19 via Cell-Based Regenerative Medicine: Lessons Learned from 1918 Spanish Flu and Other Previous Pandemics. Stem Cell Rev Rep 2021; 17:9-32. [PMID: 32789802 PMCID: PMC7423503 DOI: 10.1007/s12015-020-10026-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The human population is in the midst of battling a rapidly-spreading virus- Severe Acute Respiratory Syndrome Coronavirus 2, responsible for Coronavirus disease 2019 or COVID-19. Despite the resurgences in positive cases after reopening businesses in May, the country is seeing a shift in mindset surrounding the pandemic as people have been eagerly trickling out from federally-mandated quarantine into restaurants, bars, and gyms across America. History can teach us about the past, and today's pandemic is no exception. Without a vaccine available, three lessons from the 1918 Spanish flu pandemic may arm us in our fight against COVID-19. First, those who survived the first wave developed immunity to the second wave, highlighting the potential of passive immunity-based treatments like convalescent plasma and cell-based therapy. Second, the long-term consequences of COVID-19 are unknown. Slow-progressive cases of the Spanish flu have been linked to bacterial pneumonia and neurological disorders later in life, emphasizing the need to reduce COVID-19 transmission. Third, the Spanish flu killed approximately 17 to 50 million people, and the lack of human response, overcrowding, and poor hygiene were key in promoting the spread and high mortality. Human behavior is the most important strategy for preventing the virus spread and we must adhere to proper precautions. This review will cover our current understanding of the pathology and treatment for COVID-19 and highlight similarities between past pandemics. By revisiting history, we hope to emphasize the importance of human behavior and innovative therapies as we wait for the development of a vaccine. Graphical Abstract.
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Affiliation(s)
- You Jeong Park
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | - Jeffrey Farooq
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | - Justin Cho
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | | | - Blaise Cozene
- Tulane University, 6823 St. Charles Ave, 70118, New Orleans, LA, USA
| | | | - Madeline Saft
- University of Michigan, 500 S State St, 48109, Ann Arbor, MI, USA
| | | | | | - R Douglas Shytle
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | - Alison E Willing
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | - Svitlana Garbuzova-Davis
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | - Paul R Sanberg
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA
| | - Cesar V Borlongan
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA.
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11
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Dai W, Leng X, Wang J, Shi Z, Cheng J, Hu X, Ao Y. Intra-Articular Mesenchymal Stromal Cell Injections Are No Different From Placebo in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Arthroscopy 2021; 37:340-358. [PMID: 33098949 DOI: 10.1016/j.arthro.2020.10.016] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 10/08/2020] [Accepted: 10/08/2020] [Indexed: 02/02/2023]
Abstract
PURPOSE To evaluate the efficacy and safety of intra-articular mesenchymal stromal cells (MSCs) injections for knee osteoarthritis (OA) treatment. METHODS We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane Library through April 2020 to identify level I randomized controlled trials (RCTs) that evaluated the clinical efficacy of MSCs versus control treatments for knee OA. Outcomes were analyzed on an intention-to-treat basis with random-effects models. RESULTS A total of 13 RCTs were included in the meta-analysis. Compared with placebo, there was no significant difference in VAS for pain (mean difference [MD] 1.62, 95% confidence interval [CI -0.60 to 3.85), WOMAC pain score (MD 1.88, 95% CI -0.21 to 3.98), WOMAC function score (MD -0.67, 95% CI -6.54 to 5.19), or WOMAC stiffness score (MD 0.64, 95% CI -0.86 to 2.14) for MSCs. Moreover, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the minimum clinically important difference (MCID). Additionally, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and placebo groups for VAS for pain (relative risk [RR] 0.93, 95% CI 0.55 to 1.57) or WOMAC total score (RR 0.40, 95% CI 0.13 to 1.21). Compared with hyaluronic acid (HA), MSC injection was associated with significantly better improvement in VAS for pain (MD 2.00, 95% CI 0.94 to 3.07), WOMAC pain score (MD 4.58, 95% CI 0.49 to 8.67), WOMAC total score (MD 14.86, 95% CI 10.59 to 19.13), and WOMAC stiffness score (MD 1.85, 95% CI 0.02 to 3.69). However, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the MCID. Moreover, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and HA groups for WOMAC total score (RR 0.57, 95% CI 0.21 to 1.55). We also found that MSCs did not increase adverse events compared with HA and placebo. CONCLUSIONS Intra-articular MSC injection was not found to be superior to placebo in pain relief and functional improvement for patients with symptomatic knee OA. However, additional direct testing and combination trials of different type of cells, doses, and number of injections of MSCs are required to further enhance clinical decision making for people with symptomatic knee OA. LEVEL OF EVIDENCE I, meta-analysis of level I studies.
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Affiliation(s)
- Wenli Dai
- Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, People's Republic of China
| | - Xi Leng
- Medical Imaging Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong, People's Republic of China
| | - Jian Wang
- Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangdong, People's Republic of China
| | - Zhanjun Shi
- Department of Orthopedic Surgery, Nanfang Hospital, Southern Medical University, Guangdong, People's Republic of China
| | - Jin Cheng
- Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, People's Republic of China
| | - Xiaoqing Hu
- Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, People's Republic of China.
| | - Yingfang Ao
- Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, People's Republic of China.
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12
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Kim GB, Kim JD, Choi Y, Choi CH, Lee GW. Intra-Articular Bone Marrow Aspirate Concentrate Injection in Patients with Knee Osteoarthritis. APPLIED SCIENCES 2020; 10:5945. [DOI: 10.3390/app10175945] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/04/2024]
Abstract
We aimed to evaluate the 5-year follow-up outcomes of an intra-articular bone marrow aspirate concentrate (BMAC) injection in patients with knee osteoarthritis. This is the first study to report the outcomes following BMAC injections over a 5-year follow-up period. Seventy knees of 37 patients, including 33 bilateral knees, were investigated. The primary outcome was the visual analogue scale (VAS) score for pain in the knee joint, and the secondary outcomes were the International Knee Documentation Committee score, the 36-Item Short Form Health Survey score, the Knee injury Osteoarthritis Outcome Score, Lysholm Knee Questionnaire/Tegner activity scale, BMAC injection-induced complications, and 5-year treatment success rate. The 5-year post-injection VAS scores (4.7 ± 0.5) were significantly lower than the preoperative scores (8.3 ± 1.2) (p = 0.01). Improvement in VAS scores was significantly greater in patients with Kellgren–Lawrence (K-L) Grade I or II than those in those with K-L Grade III or IV. Improvement in other clinical parameters and success rates were significantly low and the rates of secondary operation and failure were significantly higher in patients with K-L Grades III or IV. Intra-articular BMAC injections could be useful for managing patients with K-L Grades I or II osteoarthritis.
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Affiliation(s)
- Gi Beom Kim
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea
| | - Jae-Do Kim
- Department of Orthopedic Surgery, Kosin University College of Medicine, Kosin University Gospel Hospital, 34 Amnam-dong, Seogu, Busan 602-702, Korea
| | - Young Choi
- Department of Orthopedic Surgery, Kosin University College of Medicine, Kosin University Gospel Hospital, 34 Amnam-dong, Seogu, Busan 602-702, Korea
| | - Chang Hyun Choi
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea
| | - Gun Woo Lee
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu 42415, Korea
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13
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Ntege EH, Sunami H, Shimizu Y. Advances in regenerative therapy: A review of the literature and future directions. Regen Ther 2020; 14:136-153. [PMID: 32110683 PMCID: PMC7033303 DOI: 10.1016/j.reth.2020.01.004] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/14/2020] [Accepted: 01/26/2020] [Indexed: 12/14/2022] Open
Abstract
There is enormous global anticipation for stem cell-based therapies that are safe and effective. Numerous pre-clinical studies present encouraging results on the therapeutic potential of different cell types including tissue derived stem cells. Emerging evidences in different fields of research suggest several cell types are safe, whereas their therapeutic application and effectiveness remain challenged. Multiple factors that influence treatment outcomes are proposed including immunocompatibility and potency, owing to variations in tissue origin, ex-vivo methodologies for preparation and handling of the cells. This communication gives an overview of literature data on the different types of cells that are potentially promising for regenerative therapy. As a case in point, the recent trends in research and development of the mesenchymal stem cells (MSCs) for cell therapy are considered in detail. MSCs can be isolated from a variety of tissues and organs in the human body including bone marrow, adipose, synovium, and perinatal tissues. However, MSC products from the different tissue sources exhibit unique or varied levels of regenerative abilities. The review finally focuses on adipose tissue-derived MSCs (ASCs), with the unique properties such as easier accessibility and abundance, excellent proliferation and differentiation capacities, low immunogenicity, immunomodulatory and many other trophic properties. The suitability and application of the ASCs, and strategies to improve the innate regenerative capacities of stem cells in general are highlighted among others.
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Affiliation(s)
- Edward H. Ntege
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Japan
- Research Center for Regenerative Medicine, School of Medicine, University of the Ryukyus, Japan
| | - Hiroshi Sunami
- Research Center for Regenerative Medicine, School of Medicine, University of the Ryukyus, Japan
| | - Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Japan
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14
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Deniz AAH, Abdik EA, Abdik H, Aydın S, Şahin F, Taşlı PN. Zooming in across the Skin: A Macro-to-Molecular Panorama. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1247:157-200. [PMID: 31953808 DOI: 10.1007/5584_2019_442] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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15
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Lange-Consiglio A, Gusmara C, Manfredi E, Idda A, Soggiu A, Greco V, Bonizzi L, Cremonesi F, Zecconi A. Antimicrobial Effects of Conditioned Medium From Amniotic Progenitor Cells in vitro and in vivo: Toward Tissue Regenerative Therapies for Bovine Mastitis. Front Vet Sci 2019; 6:443. [PMID: 31921904 PMCID: PMC6930869 DOI: 10.3389/fvets.2019.00443] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 11/26/2019] [Indexed: 12/27/2022] Open
Abstract
There is increasing evidence to suggest that, in addition to their regenerative effect, mesenchymal stromal cells (MSCs), and their secretome have an anti-inflammatory and antimicrobial role in the innate immune response in conditions such as sepsis. However, there is no published information on the effect of MSCs in bovine mastitis. Mastitis often results in extensive tissue damage due to multi-microorganism co-infection. This study investigated the ability of amniotic-derived conditioned medium (CM), in vitro and in vivo, to counteract microbial action and restore healthy tissue capable of milk production. Following determination of a dose–response curve, 10,000 colony-forming units (CFU) of Staphylococcus aureus (S. aureus) were inoculated into bovine mammary epithelial cell culture with and without 10% CM (supplemented either at the time of bacteria inoculation or after 4 h). Acridine orange staining was used to assess cell viability/apoptosis. Additionally, an in vivo study was performed using 48 dairy cows with acute and chronic mastitis, treated with CM (treated group) or antibiotics (control group). In vitro results showed that CM can attenuate bacterial growth, as evaluated by the number of CFU. After 24 h of culture with S. aureus, 89.67% of mammary epithelial cells treated with CM were still alive, whereas all cells cultured without CM were dead. Rates of epithelial cell survival (60.67%) were similar when CM was added 4 h after bacteria inoculation. There was no difference in somatic cell count between cases of acute mastitis in the CM-treated or control group in the in vivo study. However, relapses in chronic mastitis were less common in the group receiving CM. Our results show that CM is able to mitigate bacterial growth in vitro and may be particularly useful in the treatment of chronic mastitis, aiding restoration of milk production in cows that would otherwise be removed from the production cycle.
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Affiliation(s)
- Anna Lange-Consiglio
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy.,Reproduction Unit, Centro Clinico-Veterinario e Zootecnico-Sperimentale di Ateneo, Università degli Studi di Milano, Milan, Italy
| | - Claudia Gusmara
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy
| | | | - Antonella Idda
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy
| | - Alessio Soggiu
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy
| | - Viviana Greco
- Institute of Biochemistry and Clinical Biochemistry, Università del Sacro Cuore Roma, Rome, Italy.,Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Luigi Bonizzi
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy
| | - Fausto Cremonesi
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy.,Reproduction Unit, Centro Clinico-Veterinario e Zootecnico-Sperimentale di Ateneo, Università degli Studi di Milano, Milan, Italy
| | - Alfonso Zecconi
- Department of Veterinary Medicine (DIMEVET), Università degli Studi di Milano, Milan, Italy
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16
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Molecular characterization of bovine amniotic fluid derived stem cells with an underlying focus on their comparative neuronal potential at different passages. Ann Anat 2019; 228:151452. [PMID: 31778790 DOI: 10.1016/j.aanat.2019.151452] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 10/17/2019] [Accepted: 11/13/2019] [Indexed: 11/21/2022]
Abstract
BACKGROUND The excellence in the field of stem cell therapy demands alternative and more convenient stem cells for potential applications. Researchers have opted for least invasive and broadly multipotent cells with minimum ethical concerns. Bovine amniotic fluid derived mesenchymal stem cells (BAF-MSCs) due to their ease of collection and owing similar gestational length to that of human could be presumed as an attractive large animal model for biomedical and biotechnology research. METHODS Bovine amniotic fluid derived stem cells were isolated from abattoir based samples and characterized for epithelial, neuronal, mesenchymal and pluripotent markers by qPCR and immunofluorescence studies at P1, P3, P5 and P7 alongside population doubling time, growth curve and multilineage differentiation studies. RESULTS The cells were explored for unique expression of Sox2, which was observed to be up regulated with increase in passage number and Nestin was found to be downregulated during further passaging of mesenchymal cells in this study. The cells also co-expressed Oct ¾ at initial passages which diminished within further passages. Evidence regarding diversity and heterogeneity in different cell population in amniotic fluid was recorded by positive expression of epithelial cell markers like pan Cytokeratin and p63 during early passages. The study suggested that cells with higher expression of Sox2 generated comparatively larger neurospheres with comparative strong expression of Sox2 and Nestin by immunofluorescence staining and qPCR analysis. Besides BAF-MSCs derived neurospheres were also shown to express pro-neuronal markers like ß-III Tubulin, GAP43 and ASCL-1. CONCLUSIONS This study explores and characterizes BAF-MSCs for their multipotent and neurogenic potentials and their use for clinical applications, though more detailed studies are needed to determine the exact pathways linked with neurogenic capacities of these cells and their morphological assessments at different gestational ages in bovines. The knowledge from the bovine model after detailed studies, proven safety and efficacy could also be used to understand substitutive strategies to investigate MSCs physiology at different trimesters and potential application of these cells for human and veterinary regenerative medicine provided the animal ethics are carefully monitored.
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17
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Brown C, McKee C, Bakshi S, Walker K, Hakman E, Halassy S, Svinarich D, Dodds R, Govind CK, Chaudhry GR. Mesenchymal stem cells: Cell therapy and regeneration potential. J Tissue Eng Regen Med 2019; 13:1738-1755. [PMID: 31216380 DOI: 10.1002/term.2914] [Citation(s) in RCA: 374] [Impact Index Per Article: 62.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 05/15/2019] [Accepted: 06/07/2019] [Indexed: 12/12/2022]
Abstract
Rapid advances in the isolation of multipotent progenitor cells, routinely called mesenchymal stromal/stem cells (MSCs), from various human tissues and organs have provided impetus to the field of cell therapy and regenerative medicine. The most widely studied sources of MSCs include bone marrow, adipose, muscle, peripheral blood, umbilical cord, placenta, fetal tissue, and amniotic fluid. According to the standard definition of MSCs, these clonal cells adhere to plastic, express cluster of differentiation (CD) markers such as CD73, CD90, and CD105 markers, and can differentiate into adipogenic, chondrogenic, and osteogenic lineages in vitro. However, isolated MSCs have been reported to vary in their potency and self-renewal potential. As a result, the MSCs used for clinical applications often lead to variable or even conflicting results. The lack of uniform characterization methods both in vitro and in vivo also contributes to this confusion. Therefore, the name "MSCs" itself has been increasingly questioned lately. As the use of MSCs is expanding rapidly, there is an increasing need to understand the potential sources and specific potencies of MSCs. This review discusses and compares the characteristics of MSCs and suggests that the variations in their distinctive features are dependent on the source and method of isolation as well as epigenetic changes during maintenance and growth. We also discuss the potential opportunities and challenges of MSC research with the hope to stimulate their use for therapeutic and regenerative medicine.
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Affiliation(s)
- Christina Brown
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Christina McKee
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Shreeya Bakshi
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Keegan Walker
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - Eryk Hakman
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
| | - Sophia Halassy
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
| | - David Svinarich
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
- Ascension Providence Hospital, Southfield, MI, USA
| | - Robert Dodds
- Department of Obstetrics and Gynecology, Ascension Providence Hospital, Southfield, MI, USA
| | - Chhabi K Govind
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, MI, USA
- OU-WB Institute for Stem Cell and Regenerative Medicine, Oakland University, Rochester, MI, USA
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18
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Stem cells in Osteoporosis: From Biology to New Therapeutic Approaches. Stem Cells Int 2019; 2019:1730978. [PMID: 31281368 PMCID: PMC6589256 DOI: 10.1155/2019/1730978] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Revised: 04/21/2019] [Accepted: 04/23/2019] [Indexed: 12/11/2022] Open
Abstract
Osteoporosis is a systemic disease that affects the skeleton, causing reduction of bone density and mass, resulting in destruction of bone microstructure and increased risk of bone fractures. Since osteoporosis is a disease affecting the elderly and the aging of the world's population is constantly increasing, it is expected that the incidence of osteoporosis and its financial burden on the insurance systems will increase continuously and there is a need for more understanding this condition in order to prevent and/or treat it. At present, available drug therapy for osteoporosis primarily targets the inhibition of bone resorption and agents that promote bone mineralization, designed to slow disease progression. Safe and predictable pharmaceutical means to increase bone formation have been elusive. Stem cell therapy of osteoporosis, as a therapeutic strategy, offers the promise of an increase in osteoblast differentiation and thus reversing the shift towards bone resorption in osteoporosis. This review is focused on the current views regarding the implication of the stem cells in the cellular and physiologic mechanisms of osteoporosis and discusses data obtained from stem cell-based therapies of osteoporosis in experimental animal models and the possibility of their future application in clinical trials.
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19
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Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem Cells Transl Med 2019; 8:504-511. [PMID: 30835956 PMCID: PMC6525553 DOI: 10.1002/sctm.18-0122] [Citation(s) in RCA: 319] [Impact Index Per Article: 53.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 01/08/2019] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra-articular injection of autologous adipose-derived mesenchymal stem cells (AD-MSCs). This study aimed to assess the efficacy and safety of a single intra-articular injection of AD-MSCs for patients with knee osteoarthritis. It was a prospective double-blinded, randomized controlled, phase IIb clinical trial. AD-MSCs were administered for 12 patients (MSC group), and the group was compared with 12 knees with injection of normal saline (control group) up to 6 months. All procedures were performed in the outpatient clinic. Primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) score. Secondary outcome measure included various clinical and radiologic examination, and safety after injection. Change of cartilage defect after injection was evaluated using magnetic resonance imaging (MRI). Single injection of AD-MSCs led to a significant improvement of the WOMAC score at 6 months. In the control group, there was no significant change in the WOMAC score at 6 months. No serious adverse events were observed in both groups during the follow-up period. In MRI, there was no significant change of cartilage defect at 6 months in MSC group whereas the defect in the control group was increased. An intra-articular injection of autologous AD-MSCs provided satisfactory functional improvement and pain relief for patients with knee osteoarthritis in the outpatient setting, without causing adverse events at 6 months' follow-up. Larger sample size and long-term follow-up are required. Stem Cells Translational Medicine 2019;8:504-511.
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Affiliation(s)
- Woo-Suk Lee
- Department of Orthopaedic Surgery, College of Medicine, Gangnam Severance Hospital, Yonsei University, Seoul, South Korea
| | - Hwan Jin Kim
- Department of Orthopaedic Surgery, Center for Joint Diseases and Rheumatism, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.,School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Kang-Il Kim
- Department of Orthopaedic Surgery, Center for Joint Diseases and Rheumatism, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.,School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Gi Beom Kim
- Department of Orthopaedic Surgery, Center for Joint Diseases and Rheumatism, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.,School of Medicine, Kyung Hee University, Seoul, South Korea
| | - Wook Jin
- Department of Radiology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea
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20
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Hawsawi YM, Al-Zahrani F, Mavromatis CH, Baghdadi MA, Saggu S, Oyouni AAA. Stem Cell Applications for Treatment of Cancer and Autoimmune Diseases: Its Promises, Obstacles, and Future Perspectives. Technol Cancer Res Treat 2019; 17:1533033818806910. [PMID: 30343639 PMCID: PMC6198389 DOI: 10.1177/1533033818806910] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Since the original discovery of stem cells, a new era of promising results has emerged in the clinical application of stem cells for the treatment of several important diseases, including cancer and autoimmune diseases. The plentiful research on stem cells during the past decades has provided significant information on the developmental, morphological, and physiological processes that govern tissue and organ formation, maintenance, and regeneration; cellular differentiation; molecular processes; and tissue homeostasis. In this review, we present the history of the use of stem cells in different clinical applications. Furthermore, we discuss the various therapeutic options for stem cells in cancer, followed by the role of stem cells in the treatment of autoimmune disorders. Additionally, we highlight the risks of and obstacles to the application of stem cells in clinical practice. Ultimately, we show future perspectives in stem cell use, with an aim to improve the clinical usefulness of stem cells.
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Affiliation(s)
- Yousef M Hawsawi
- 1 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.,2 Department of Biological Sciences, Faculty of Science and Arts, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia.,3 Department of Epidemiology and Biostatistics, King Faisal Specialist Hospital and Research Center, Jeddah, Kingdom of Saudi Arabia
| | - Faisal Al-Zahrani
- 2 Department of Biological Sciences, Faculty of Science and Arts, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia
| | - Charalampos Harris Mavromatis
- 2 Department of Biological Sciences, Faculty of Science and Arts, King Abdulaziz University, Rabigh, Kingdom of Saudi Arabia
| | - Mohammed A Baghdadi
- 1 Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.,3 Department of Epidemiology and Biostatistics, King Faisal Specialist Hospital and Research Center, Jeddah, Kingdom of Saudi Arabia
| | - Shalini Saggu
- 4 Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Kingdom of Saudi Arabia
| | - Atif Abdulwahab A Oyouni
- 4 Department of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Kingdom of Saudi Arabia
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Kargozar S, Mozafari M, Hamzehlou S, Brouki Milan P, Kim HW, Baino F. Bone Tissue Engineering Using Human Cells: A Comprehensive Review on Recent Trends, Current Prospects, and Recommendations. APPLIED SCIENCES 2019; 9:174. [DOI: 10.3390/app9010174] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The use of proper cells for bone tissue engineering remains a major challenge worldwide. Cells play a pivotal role in the repair and regeneration of the bone tissue in vitro and in vivo. Currently, a large number of differentiated (somatic) and undifferentiated (stem) cells have been used for bone reconstruction alone or in combination with different biomaterials and constructs (e.g., scaffolds). Although the results of the cell transplantation without any supporting or adjuvant material have been very effective with regard to bone healing. Recent advances in bone scaffolding are now becoming new players affecting the osteogenic potential of cells. In the present study, we have critically reviewed all the currently used cell sources for bone reconstruction and discussed the new horizons that are opening up in the context of cell-based bone tissue engineering strategies.
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Affiliation(s)
- Saeid Kargozar
- Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad 917794-8564, Iran
| | - Masoud Mozafari
- Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran 14155-4777, Iran
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran 144961-4535, Iran
| | - Sepideh Hamzehlou
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran 14155-6447, Iran
- Medical Genetics Network (MeGeNe), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Peiman Brouki Milan
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran 144961-4535, Iran
| | - Hae-Won Kim
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, Korea
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 31116, Korea
- Department of Nanobiomedical Science & BK21 PLUS NBM Global Research Center for Regenerative Medicine Research Center, Dankook University, Cheonan 31116, Korea
| | - Francesco Baino
- Institute of Materials Physics and Engineering, Applied Science and Technology Department, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino, Italy
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Arjmand B, Goodarzi P, Aghayan HR, Payab M, Rahim F, Alavi-Moghadam S, Mohamadi-jahani F, Larijani B. Co-transplantation of Human Fetal Mesenchymal and Hematopoietic Stem Cells in Type 1 Diabetic Mice Model. Front Endocrinol (Lausanne) 2019; 10:761. [PMID: 31781036 PMCID: PMC6856665 DOI: 10.3389/fendo.2019.00761] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Accepted: 10/21/2019] [Indexed: 12/12/2022] Open
Abstract
Introduction: Cell therapy can overcome the limitation of conventional treatments (including different medications and β cell replacement) for type 1 diabetes. Based- on several studies human fetal mesenchymal and hematopoietic stem cells are ideal candidates for stem cell therapy. On the other hand, co-transplantation of them can improve their effects. Accordingly, the aim of this research is co-transplantation of human fetal mesenchymal and hematopoietic stem cells in type 1 diabetes. Materials and Methods: The liver of legally aborted fetus was harvested. Then, mononuclear cells were isolated and extracted mesenchymal stromal cells and CD34+ hematopoietic stem cells were cultured. Expression of pluripotency markers were evaluated. For molecular imaging, mesenchymal stromal cells were labeled using GFP- vector. BALB/c inbred male mice were modeled by injection a single dose of Streptozotocin. Diabetic animals were received stem cells. After stem cell transplantation, in vivo imaging was performed and blood glucose levels were measured weekly. Results: Fetal mesenchymal stromal cells were demonstrated differentiation potential. Expression of pluripotency markers were positive. The mean of blood glucose levels were reduced in mixed mesenchymal and hematopoietic stem cells transplantation. A lot of GFP-labeled mesenchymal stem cells were engrafted in the pancreas of animal models that received a mixed suspension of hematopoietic and mesenchymal stromal cells. Conclusions: Human fetal stem cells are valuable source for cell therapy and co-transplantation of mesenchymal stromal cells can improve therapeutic effects of hematopoietic stem cells.
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Affiliation(s)
- Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Reza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moloud Payab
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fakher Rahim
- Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sepideh Alavi-Moghadam
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereshteh Mohamadi-jahani
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Bagher Larijani ;
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Kubsik-Gidlewska A, Klupiński K, Krochmalski M, Krochmalski J, Klimkiewicz P, Woldańska-Okońska M. CD34+ Stem Cell Treatment for Knee Osteoarthritis: A Treatment and Rehabilitation Algorithm. JOURNAL OF REHABILITATION MEDICINE - CLINICAL COMMUNICATIONS 2018; 3:1000012. [PMID: 33884126 PMCID: PMC8011677 DOI: 10.2340/20030711-1000012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Accepted: 11/14/2018] [Indexed: 11/24/2022]
Abstract
Osteoarthritis is a group of multiple overlapping pathological conditions that cause destruction of articular cartilage and other structures of the joint. It is a progressive disease that leads to limitations of physical activity. New forms of treatment are therefore sought to alleviate the clinical symptoms of osteoarthritis and avoid surgery. Stem cell based therapy is an emerging field in orthopaedics. This study describes the treatment of knee osteoarthritis with CD34+ stem cells at the Medical Magnus Outpatient Clinic in Lodz, Poland, together with the treatment and rehabilitation algorithm developed for maximum effectiveness of this procedure. The algorithm includes 3 rehabilitation stages: preoperative, hospitalization and outpatient periods.
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