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Chang DW, Wu CC, Liu FL, Lu CC, Chu CC, Chang DM. Fetal microchimerism cells suppress arthritis progression by inducing CD14+ IL-10+ cells in pregnant experimental mice. Int J Rheum Dis 2024; 27:e15322. [PMID: 39221919 DOI: 10.1111/1756-185x.15322] [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: 06/19/2024] [Revised: 07/20/2024] [Accepted: 08/17/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Fetal microchimerism occurs in the mother after a pregnancy. To investigate the role of fetal microchimerism cells (FMCs) in rheumatoid arthritis, we analyzed the population of fetal cells in pregnant experimental arthritis mice. METHODS We used EGFP+ fetuses, which were mated with either healthy female mice or CIA mice, and male C57BL/6J-Tg (Pgk1-EGFP)03Narl mice, to detect the population of FMCs in maternal circulation. The disease progression was determined by measuring the clinical score and histological stains during pregnancy. The fetal cells have been analyzed if expressing EGFP, CD45, and Scal by flow cytometry. We also detected the expression of CD14+ IL-10+ cells in vivo and in vitro. RESULTS Our data showed that the pregnancy ameliorated the arthritis progression of CIA mice. The IHC stains showed the CD45 -Sca-1+ EGFP+ FMCs were expressed in the bone marrow and peripheral blood mononuclear cells (PBMC) at 14 gestation days. However, Treg and Tc cell populations showed no significant change in the bone marrow. The data showed the H2Kb + fetal cells induced CD14+ IL10+ cell populations increased in the bone marrow in vitro and in vivo. CONCLUSION Our investigations demonstrated that the FMCs protected the CIA mice from cartilage damage and triggered an immunosuppressive response in them by increasing the number of CD14+ IL10+ cells. In conclusion, the FMCs could potentially exhibit protective properties within the context of inflammatory arthritis that arises during pregnancy.
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Affiliation(s)
- Da-Wei Chang
- Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Cheng-Chi Wu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Fei-Lan Liu
- Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Chun-Chi Lu
- Division of Allergy/Immunology/Rheumatology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Chen-Chih Chu
- Division of Allergy/Immunology/Rheumatology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
| | - Deh-Ming Chang
- Division of Allergy/Immunology/Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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2
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Murata D, Kunitomi Y, Harada K, Tokunaga S, Takao S, Nakayama K. Osteochondral regeneration using scaffold-free constructs of adipose tissue-derived mesenchymal stem cells made by a bio three-dimensional printer with a needle-array in rabbits. Regen Ther 2020; 15:77-89. [PMID: 33426205 PMCID: PMC7770347 DOI: 10.1016/j.reth.2020.05.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 04/24/2020] [Accepted: 05/03/2020] [Indexed: 12/15/2022] Open
Abstract
Osteoarthritis is a major joint disease for which medical interventions have been extensively investigated in humans and animals. In this study, we examined the regeneration of articular cartilage and subchondral bone using a scaffold-free construct consisting of adipose tissue-derived mesenchymal stem cells (AT-MSCs) fabricated using a bio three-dimensional (3D) printer. AT-MSCs were isolated from three rabbits and cultured to a number of sufficient for creation of 3D-printed constructs. One construct consisted of 960 spheroids obtained from 3.5 × 104 autologous AT-MSCs. The construct was then implanted into an osteochondral defect (diameter 4 mm and depth 4 mm) surgically bored into the left femoral trochlear groove of each rabbit. Three months after implantation, healing was assessed by computed tomography, magnetic resonance (MR) imaging, and pathology. MR images were evaluated based on a modified two-dimensional (2D)-magnetic resonance observation of cartilage repair tissue (MOCART) grading system, and gross and microscopic histology were scored according to the International Cartilage Repair Society scale. At the time of imaging, treated defects had become radiopaque, while control defects remained radiolucent. Total 2D-MOCART scores were higher in the implanted defects than in the controls, but not to a statistically significant extent. Similarly, average histological scores were comparable among all groups, although average gross scores were significantly higher in implanted defects than in controls. This is the first demonstration of a scaffold-free 3D-printed construct consisting of autologous AT-MSCs regenerating cartilage and subchondral bone within three months.
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Affiliation(s)
- Daiki Murata
- Veterinary Surgery, Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.,Center for Regenerative Medicine Research, Faculty of Medicine, Saga University, Saga, Japan
| | | | - Kaori Harada
- Cyfuse Biomedical K.K., 3-1 Hongo 7-chome, Bunkyo-ku, Tokyo, Japan
| | - Satoshi Tokunaga
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.,Veterinary Teaching Hospital, College of Veterinary Medicine and Biomedical Science, Colorado State University, Fort Collins, CO, USA
| | - Shoko Takao
- Center for Regenerative Medicine Research, Faculty of Medicine, Saga University, Saga, Japan
| | - Koichi Nakayama
- Center for Regenerative Medicine Research, Faculty of Medicine, Saga University, Saga, Japan
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3
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Terraza-Aguirre C, Campos-Mora M, Elizondo-Vega R, Contreras-López RA, Luz-Crawford P, Jorgensen C, Djouad F. Mechanisms behind the Immunoregulatory Dialogue between Mesenchymal Stem Cells and Th17 Cells. Cells 2020; 9:cells9071660. [PMID: 32664207 PMCID: PMC7408034 DOI: 10.3390/cells9071660] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 07/03/2020] [Accepted: 07/05/2020] [Indexed: 12/18/2022] Open
Abstract
Mesenchymal stem cells (MSCs) exhibit potent immunoregulatory abilities by interacting with cells of the adaptive and innate immune system. In vitro, MSCs inhibit the differentiation of T cells into T helper 17 (Th17) cells and repress their proliferation. In vivo, the administration of MSCs to treat various experimental inflammatory and autoimmune diseases, such as rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and bowel disease showed promising therapeutic results. These therapeutic properties mediated by MSCs are associated with an attenuated immune response characterized by a reduced frequency of Th17 cells and the generation of regulatory T cells. In this manuscript, we review how MSC and Th17 cells interact, communicate, and exchange information through different ways such as cell-to-cell contact, secretion of soluble factors, and organelle transfer. Moreover, we discuss the consequences of this dynamic dialogue between MSC and Th17 well described by their phenotypic and functional plasticity.
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Affiliation(s)
- Claudia Terraza-Aguirre
- IRMB, University of Montpellier, INSERM, F-34090 Montpellier, France; (C.T.-A.); (R.A.C.-L.)
| | | | - Roberto Elizondo-Vega
- Facultad de Ciencias Biológicas, Departamento de Biología Celular, Laboratorio de Biología Celular, Universidad de Concepción, Concepción 4030000, Chile;
| | | | - Patricia Luz-Crawford
- Centro de Investigación Biomédica, Facultad de Medicina, Universidad de Los Andes, Santiago 7620001, Chile;
| | - Christian Jorgensen
- IRMB, University of Montpellier, INSERM, F-34090 Montpellier, France; (C.T.-A.); (R.A.C.-L.)
- CHU Montpellier, F-34295 Montpellier, France
- Correspondence: (C.J.); (F.D.); Tel.: +33-(0)-4-67-33-77-96 (C.J.); +33-(0)-4-67-33-04-75 (F.D.)
| | - Farida Djouad
- IRMB, University of Montpellier, INSERM, F-34090 Montpellier, France; (C.T.-A.); (R.A.C.-L.)
- Correspondence: (C.J.); (F.D.); Tel.: +33-(0)-4-67-33-77-96 (C.J.); +33-(0)-4-67-33-04-75 (F.D.)
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4
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Zhao Y, Zhu T, Li H, Zhao J, Li X. Transplantation of Lymphocytes Co-Cultured with Human Cord Blood-Derived Multipotent Stem Cells Attenuates Inflammasome Activity in Ischemic Stroke. Clin Interv Aging 2019; 14:2261-2271. [PMID: 31908436 PMCID: PMC6927491 DOI: 10.2147/cia.s223595] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 12/11/2019] [Indexed: 01/25/2023] Open
Abstract
Background Manipulating the immune inflammatory response after cerebral ischemia has been a novel therapeutic strategy for ischemic stroke. This study attempted to investigate the effects of the transplantation of lymphocytes co-cultured with human cord blood-derived multipotent stem cells (HCB-SCs) on the inflammatory response in transient middle cerebral occlusion (tMCAO) rats. Methods The tMCAO rats were subjected to the transplantation of lymphocytes co-cultured with HCB-SCs through tail vein injection. Infarct size and neurological deficits were measured at 48 hrs after stroke. Neurological deficits were assessed using Bederson’s scoring system and tape removal test. Blood T cell flow cytometry was performed to measure the differentiation of regulatory T cells (Tregs). Western blot was used to detect the protein levels of inflammation-related molecules, apoptosis-related molecule, and signaling molecules in ischemic brain. TUNEL staining was performed to analyze cell apoptosis in ischemic cerebral cortex. Results The transplantation of lymphocytes co-cultured with HCB-SCs significantly improved the neurological defects, reduced ischemic brain damage, and increased the proportion of peripheral CD4+CD25+Foxp3+ Tregs. Meanwhile, the transplantation of co-cultured cells decreased the expression of NLRP3 inflammasome and associated factors, such as caspase-1 and IL-1β, and inhibited the activation of NF-κB, ERK and caspase-3 in ischemic brain. The co-cultured cells significantly decreased the number of tMCAO-induced cell apoptosis. Conclusion Lymphocytes co-cultured with HCB-SCs exhibit a neuroprotective effect after ischemic stroke by promoting Tregs differentiation and suppressing NLRP3 inflammasome activation and neuron apoptosis, and might be a promising therapeutic strategy for ischemic stroke.
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Affiliation(s)
- Yanxin Zhao
- Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, People's Republic of China
| | - Tianrui Zhu
- Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, People's Republic of China
| | - Heng Li
- Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, People's Republic of China
| | - Jing Zhao
- Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, People's Republic of China
| | - Xiaohong Li
- Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, People's Republic of China
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Stiner R, Alexander M, Liu G, Liao W, Liu Y, Yu J, Pone EJ, Zhao W, Lakey JRT. Transplantation of stem cells from umbilical cord blood as therapy for type I diabetes. Cell Tissue Res 2019; 378:155-162. [PMID: 31209568 DOI: 10.1007/s00441-019-03046-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Accepted: 04/21/2019] [Indexed: 12/15/2022]
Abstract
In recent years, human umbilical cord blood has emerged as a rich source of stem, stromal and immune cells for cell-based therapy. Among the stem cells from umbilical cord blood, CD45+ multipotent stem cells and CD90+ mesenchymal stem cells have the potential to treat type I diabetes mellitus (T1DM), to correct autoimmune dysfunction and replenish β-cell numbers and function. In this review, we compare the general characteristics of umbilical cord blood-derived multipotent stem cells (UCB-SCs) and umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and introduce their applications in T1DM. Although there are some differences in surface marker expression between UCB-SCs and UCB-MSCs, the two cell types display similar functions such as suppressing function of stimulated lymphocytes and imparting differentiation potential to insulin-producing cells (IPCs) in the setting of low immunogenicity, thereby providing a promising and safe approach for T1DM therapy.
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Affiliation(s)
- Rachel Stiner
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Surgery, University of California, Irvine, 333 City Boulevard West, Suite 1600, Orange, CA, 92868, USA
| | - Michael Alexander
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Surgery, University of California, Irvine, 333 City Boulevard West, Suite 1600, Orange, CA, 92868, USA.,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA
| | - Guangyang Liu
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Surgery, University of California, Irvine, 333 City Boulevard West, Suite 1600, Orange, CA, 92868, USA.,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA.,Baylx, Inc., 23 Spectrum Pointe Dr Suite 207, Lake Forest, CA, 92630, USA
| | - Wenbin Liao
- Baylx, Inc., 23 Spectrum Pointe Dr Suite 207, Lake Forest, CA, 92630, USA
| | - Yongjun Liu
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA.,Baylx, Inc., 23 Spectrum Pointe Dr Suite 207, Lake Forest, CA, 92630, USA.,Department of Pharmaceutical Sciences, University of California, Irvine, 147 Bison Modular, Irvine, CA, 92697, USA
| | - Jingxia Yu
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Surgery, University of California, Irvine, 333 City Boulevard West, Suite 1600, Orange, CA, 92868, USA.,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA.,Baylx, Inc., 23 Spectrum Pointe Dr Suite 207, Lake Forest, CA, 92630, USA
| | - Egest J Pone
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA.,Department of Pharmaceutical Sciences, University of California, Irvine, 147 Bison Modular, Irvine, CA, 92697, USA.,Chao Family Comprehensive Cancer Center, University of California, Irvine, 101 The City Dr S, Orange, CA, 92868, USA.,Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA
| | - Weian Zhao
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA.,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA.,Baylx, Inc., 23 Spectrum Pointe Dr Suite 207, Lake Forest, CA, 92630, USA.,Department of Pharmaceutical Sciences, University of California, Irvine, 147 Bison Modular, Irvine, CA, 92697, USA.,Chao Family Comprehensive Cancer Center, University of California, Irvine, 101 The City Dr S, Orange, CA, 92868, USA.,Department of Biological Chemistry, University of California, Irvine, Irvine, CA, 92697, USA
| | - Jonathan R T Lakey
- Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, 845 Health Sciences Road, Irvine, CA, 92697, USA. .,Department of Surgery, University of California, Irvine, 333 City Boulevard West, Suite 1600, Orange, CA, 92868, USA. .,Department of Biomedical Engineering, University of California, Irvine, 402 E Peltason Dr, Irvine, CA, 92697, USA. .,Baylx, Inc., 23 Spectrum Pointe Dr Suite 207, Lake Forest, CA, 92630, USA.
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6
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Yamasaki A, Kunitomi Y, Murata D, Sunaga T, Kuramoto T, Sogawa T, Misumi K. Osteochondral regeneration using constructs of mesenchymal stem cells made by bio three-dimensional printing in mini-pigs. J Orthop Res 2019; 37:1398-1408. [PMID: 30561041 DOI: 10.1002/jor.24206] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 12/06/2018] [Indexed: 02/04/2023]
Abstract
Osteoarthritis is a major joint disease that has been extensively investigated in humans and in model animals. In this study, we examined the regeneration of articular cartilage and subchondral bone using artificial scaffold-free constructs composed of adipose tissue-derived mesenchymal stem cells (AT-MSCs) created using bio three-dimensional (3D) printing with a needle-array. Printed constructs were implanted into osteochondral defects created in the right femoral trochlear groove of six mini-pigs, using femoral defects created in the left femurs as controls. Repair within the defects was evaluated at 3 and 6 months post-implantation using computed tomography (CT) and magnetic resonance (MR) imaging. The radiolucent volume (RV, mm3 ) in the defects was calculated using multi-planar reconstruction of CT images. MR images were evaluated based on a modified 2D- MOCART (magnetic resonance observation of cartilage repair tissue) grading system. Gross and microscopic pathology were scored according to the ICRS (International Cartilage Repair Society) scale at 6 months after implantation. The percentage RV at 3 months postoperation was significantly lower in the implanted defects than in the controls, whereas total scores based on the MOCART system were significantly higher in the implanted defects as compared with the controls. Although there were no statistical differences in the gross scores, the average histological scores were significantly higher in the implanted defects than in the controls. To our knowledge, this is the first report to suggest that artificial scaffold-free 3D-printed constructs of autologous AT-MSCs can be aid in the osteochondral regeneration in pigs. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1398-1408, 2019.
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Affiliation(s)
- Atsushi Yamasaki
- Veterinary Surgery, Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, 21-24 Korimoto 1-chome, Kagoshima, 890-0065, Japan
| | - Yoshihiro Kunitomi
- Cyfuse Biomedical K.K., 3-1 Hongo 7-chome, Bunkyo-ku, Tokyo, 113-0033, Japan
| | - Daiki Murata
- Department of Regenerative Medicine and Biomedical Engineering, Faculty of Medicine, Saga University, Honjyo 1-chome, Honjyo-cho, Saga, 840-8502, Japan
| | - Takafumi Sunaga
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, 21-24 Korimoto 1-chome, Kagoshima, 890-0065, Japan
| | - Tomohide Kuramoto
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, 21-24 Korimoto 1-chome, Kagoshima, 890-0065, Japan
| | - Takeshi Sogawa
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University, 21-24 Korimoto 1-chome, Kagoshima, 890-0065, Japan
| | - Kazuhiro Misumi
- Veterinary Surgery, Department of Veterinary Clinical Science, Joint Faculty of Veterinary Medicine, Kagoshima University, 21-24 Korimoto 1-chome, Kagoshima, 890-0065, Japan
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7
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Han X, Chen Y, Liu Y, Wang Z, Tang G, Tian W. HIF‐1α promotes bone marrow stromal cell migration to the injury site and enhances functional recovery after spinal cord injury in rats. J Gene Med 2018; 20:e3062. [PMID: 30414229 DOI: 10.1002/jgm.3062] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 10/30/2018] [Accepted: 10/31/2018] [Indexed: 12/15/2022] Open
Affiliation(s)
- Xiaoguang Han
- Department of Spine SurgeryBeijing Jishuitan Hospital Beijing China
| | - Yong Chen
- Orthopedic CenterKunshan Hospital of Traditional Chinese Medicine Kunshan China
| | - Yajun Liu
- Department of Spine SurgeryBeijing Jishuitan Hospital Beijing China
| | - Zhuo Wang
- Orthopedic CenterKunshan Hospital of Traditional Chinese Medicine Kunshan China
| | - Guoqing Tang
- Orthopedic CenterKunshan Hospital of Traditional Chinese Medicine Kunshan China
| | - Wei Tian
- Department of Spine SurgeryBeijing Jishuitan Hospital Beijing China
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Gao L, Xu W, Li T, Chen J, Shao A, Yan F, Chen G. Stem Cell Therapy: A Promising Therapeutic Method for Intracerebral Hemorrhage. Cell Transplant 2018; 27:1809-1824. [PMID: 29871521 PMCID: PMC6300771 DOI: 10.1177/0963689718773363] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 03/09/2018] [Accepted: 04/02/2018] [Indexed: 12/28/2022] Open
Abstract
Spontaneous intracerebral hemorrhage (ICH) is one type of the most devastating cerebrovascular diseases worldwide, which causes high morbidity and mortality. However, efficient treatment is still lacking. Stem cell therapy has shown good neuroprotective and neurorestorative effect in ICH and is a promising treatment. In this study, our aim was to review the therapeutic effects, strategies, related mechanisms and safety issues of various types of stem cell for ICH treatment. Numerous studies had demonstrated the therapeutic effects of diverse stem cell types in ICH. The potential mechanisms include tissue repair and replacement, neurotrophy, promotion of neurogenesis and angiogenesis, anti-apoptosis, immunoregulation and anti-inflammation and so forth. The microenvironment of the central nervous system (CNS) can also influence the effects of stem cell therapy. The detailed therapeutic strategies for ICH treatment such as cell type, the number of cells, time window, and the routes of medication delivery, varied greatly among different studies and had not been determined. Moreover, the safety issues of stem cell therapy for ICH should not be ignored. Stem cell therapy showed good therapeutic effect in ICH, making it a promising treatment. However, safety should be carefully evaluated, and more clinical trials are required before stem cell therapy can be extensively applied to clinical use.
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Affiliation(s)
- Liansheng Gao
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Weilin Xu
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Tao Li
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Jingyin Chen
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Anwen Shao
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Feng Yan
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
| | - Gao Chen
- Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China
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9
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Wang T, Wen Y, Fan X. Myeloid-derived suppressor cells suppress CD4+ T cell activity and prevent the development of type 2 diabetes. Acta Biochim Biophys Sin (Shanghai) 2018. [PMID: 29514172 DOI: 10.1093/abbs/gmy014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
CD4+ T cells play an important role in the progression of type 2 diabetes mellitus (T2DM). It is known that T cell responses can be suppressed by myeloid-derived suppressor cells (MDSCs). In this study, we aimed to explore the potential role of MDSCs in the progression of T2DM, and to examine whether the underlying mechanism was associated with CD4+ T cells. Peripheral blood samples were obtained from T2DM patients and healthy controls, as well as C57BL6J db/db mice and control heterozygous (db/-) mice. The frequency of MDSCs and CD4+ T cells was analyzed using flow cytometry. Serum levels of the cytokines interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were quantified using ELISA kits. Cell proliferation was assessed using carboxyfluorescein succinimidyl ester (CFSE) labeling. In addition, the severity of insulitis was assessed using H&E staining of the pancreata. The data showed an increased frequency of CD11b+/CD33+ MDSCs and CD4+ T cells in the peripheral blood of T2DM patients. In addition, there were decreased IL-4 level and increased TNF-α and IFN-γ levels in the serum from T2DM patients. In db/db mice, an increased frequency of CD11b+/Gr-1+ MDSCs and CD4+ T cells was found in splenocytes, as well as in the peripheral blood. MDSCs inhibited the proliferation and modulated the cytokine secretion of CD4+ T cells in vitro and delayed the development of diabetes in NOD/SCID mice. In conclusion, MDSCs suppress CD4+ T cell activity and prevent the development of T2DM.
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10
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Asgari HR, Akbari M, Yazdekhasti H, Rajabi Z, Navid S, Aliakbari F, Abbasi N, Aval FS, Shams A, Abbasi M. Comparison of Human Amniotic, Chorionic, and Umbilical Cord Multipotent Mesenchymal Stem Cells Regarding Their Capacity for Differentiation Toward Female Germ Cells. Cell Reprogram 2017; 19:44-53. [PMID: 28112985 DOI: 10.1089/cell.2016.0035] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Placenta harbors a plentiful source of various cells with stem cells or stem-like cell properties, which can be used in therapeutic procedures and research. Mesenchymal stem cells (MSCs) have attracted much attention due to their specific differentiation potential and tolerogenic properties. MSCs have been isolated from different parts of placenta; however, in this study, we isolated MSCs from amnion and chorion membrane, as well as umbilical cord (Wharton's jelly [WJ]) and compared their capacity regarding differentiation toward female germ cells under influence of 10 ng/mL BMP4. All placenta samples were collected from delivering mothers by normal cesarean section and cells were isolated by different methods. Results showed that all isolated cells were mostly positive for the MSC markers CD73, CD166, and CD105, and minimally reacted with CD34 and CD45 (hematopoietic markers). After differentiation induction using third passage cultured cells, immunocytochemistry staining showed that cells were positive for germline cell-related genes Ssea4, Oct4, and Ddx4, and oocyte-related gene Gdf9. RT-qPCR results indicated that human chorion MSCs (hCMSCs) had a greater potential to be differentiated into female germline cells. Moreover, the results of this study indicate that human umbilical cord MSCs originated from either male or female umbilical cord have the same differentiation potential into female germline cells. We recommend that for presumptive application of MSCs for infertility treatment and research, hUMSCs are best candidates due to their higher differentiation potential, ease of proliferation and expansion, and low immunogenicity.
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Affiliation(s)
- Hamid Reza Asgari
- 1 Department of Anatomy, Faculty of Medicine, Iran University of Medical Sciences , Tehran, Iran
| | - Mohammad Akbari
- 2 Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences , Tehran, Iran
| | - Hossein Yazdekhasti
- 2 Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences , Tehran, Iran
| | - Zahra Rajabi
- 2 Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences , Tehran, Iran
| | - Shadan Navid
- 2 Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences , Tehran, Iran
| | - Fereshte Aliakbari
- 2 Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences , Tehran, Iran
| | - Niloufar Abbasi
- 3 Emergency Department of Vali-e-Asr Hospital, Brojen, Shahrekord University of Medical Sciences , Shahrekord, Iran
| | - Freidon Sargolzaei Aval
- 4 Department of Anatomy, School of Medicine, Zahedan University of Medical Sciences , Zahedan, Iran
| | - Alireza Shams
- 5 Department of Anatomy, School of Medicine, Alborz University of Medical Sciences , Karaj, Iran
| | - Mehdi Abbasi
- 2 Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences , Tehran, Iran
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Borlongan CV, Yu G, Matsukawa N, Yasuhara T, Hara K, Xu L. Article Commentary: Cell Transplantation: Stem Cells in the Spotlight. Cell Transplant 2017; 14:519-526. [DOI: 10.3727/000000005783982774] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Affiliation(s)
- Cesar V. Borlongan
- Neurology/Insttitute of Molecular Medicind & Genetics/School of Graduate Studies, Medical College of Georgia, Augusta, GA, USA
- Research/Affiliations Service Line, Augusta VAMC, Augusta, GA, USA
| | - Guolong Yu
- Neurology/Insttitute of Molecular Medicind & Genetics/School of Graduate Studies, Medical College of Georgia, Augusta, GA, USA
- Research/Affiliations Service Line, Augusta VAMC, Augusta, GA, USA
| | - Noriyuki Matsukawa
- Neurology/Insttitute of Molecular Medicind & Genetics/School of Graduate Studies, Medical College of Georgia, Augusta, GA, USA
- Research/Affiliations Service Line, Augusta VAMC, Augusta, GA, USA
| | - Takao Yasuhara
- Neurology/Insttitute of Molecular Medicind & Genetics/School of Graduate Studies, Medical College of Georgia, Augusta, GA, USA
- Research/Affiliations Service Line, Augusta VAMC, Augusta, GA, USA
| | - Koichi Hara
- Neurology/Insttitute of Molecular Medicind & Genetics/School of Graduate Studies, Medical College of Georgia, Augusta, GA, USA
- Research/Affiliations Service Line, Augusta VAMC, Augusta, GA, USA
| | - Lin Xu
- Neurology/Insttitute of Molecular Medicind & Genetics/School of Graduate Studies, Medical College of Georgia, Augusta, GA, USA
- Research/Affiliations Service Line, Augusta VAMC, Augusta, GA, USA
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Sanberg PR, Greene-Zavertnik C, Davis CD. Article Commentary: Cell Transplantation: The Regenerative Medicine Journal. A Biennial Analysis of Publications. Cell Transplant 2017; 12:815-825. [DOI: 10.3727/000000003771000165] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Paul R. Sanberg
- Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., MDC 78, Tampa, FL 33612
| | - Cathryn Greene-Zavertnik
- Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., MDC 78, Tampa, FL 33612
| | - Cyndy D. Davis
- Center of Excellence for Aging and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., MDC 78, Tampa, FL 33612
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Abstract
The ischemia-induced death of cardiomyocytes results in scar formation and reduced contractility of the ventricle. Several preclinical and clinical studies have supported the notion that cell therapy may be used for cardiac regeneration. Most attempts for cardiomyoplasty have considered the bone marrow as the source of the “repair stem cell(s),” assuming that the hematopoietic stem cell can do the work. However, bone marrow is also the residence of other progenitor cells, including mesenchymal stem cells (MSCs). Since 1995 it has been known that under in vitro conditions, MSCs differentiate into cells exhibiting features of cardiomyocytes. This pioneer work was followed by many preclinical studies that revealed that ex vivo expanded, bone marrow–derived MSCs may represent another option for cardiac regeneration. In this work, we review evidence and new prospects that support the use of MSCs in cardiomyoplasty.
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Affiliation(s)
- José J Minguell
- Laboratorio de Trasplante de Médula Osea, Clínica Las Condes, Lo Fontecilla 441, Las Condes, Santiago, Chile.
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De Becker A, Riet IV. Homing and migration of mesenchymal stromal cells: How to improve the efficacy of cell therapy? World J Stem Cells 2016; 8:73-87. [PMID: 27022438 PMCID: PMC4807311 DOI: 10.4252/wjsc.v8.i3.73] [Citation(s) in RCA: 353] [Impact Index Per Article: 39.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2015] [Revised: 12/24/2015] [Accepted: 01/29/2016] [Indexed: 02/07/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC homing has been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.
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Electrospun poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/hydroxyapatite scaffold with unrestricted somatic stem cells for bone regeneration. ASAIO J 2016; 61:357-65. [PMID: 25710767 DOI: 10.1097/mat.0000000000000205] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The combination of scaffolds and cells can be useful in tissue reconstruction. In this study, nanofibrous poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/nanohydroxyapatite (nano-HAp) scaffolds, filled with unrestricted somatic stem cells (USSCs), were used for healing calvarial bone in rat model. The healing effects of these scaffolds, with and without stem cells, in bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. The results of CT analysis showed that bone regeneration on the scaffolds, and the amounts of regenerated new bone for polymer/nano-HAp scaffold with USSC, was significantly greater than the scaffold without cell and untreated control samples. Therefore, the combination of scaffold especially with USSC could be considered as a useful method for bone regeneration.
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16
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Marrow-Derived Mesenchymal Stromal Cells in the Treatment of Stroke. Transl Neurosci 2016. [DOI: 10.1007/978-1-4899-7654-3_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
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17
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Organ-specific migration of mesenchymal stromal cells: Who, when, where and why? Immunol Lett 2015; 168:159-69. [DOI: 10.1016/j.imlet.2015.06.019] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2015] [Revised: 06/17/2015] [Accepted: 06/23/2015] [Indexed: 12/13/2022]
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18
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Impact of umbilical cord blood-derived mesenchymal stem cells on cardiovascular research. BIOMED RESEARCH INTERNATIONAL 2015; 2015:975302. [PMID: 25861654 PMCID: PMC4377460 DOI: 10.1155/2015/975302] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Accepted: 01/11/2015] [Indexed: 01/06/2023]
Abstract
Over the years, cell therapy has become an exciting opportunity to treat human diseases. Early enthusiasm using adult stem cell sources has been tempered in light of preliminary benefits in patients. Considerable efforts have been dedicated, therefore, to explore alternative cells such as those extracted from umbilical cord blood (UCB). In line, UCB banking has become a popular possibility to preserve potentially life-saving cells that are usually discarded after birth, and the number of UCB banks has grown worldwide. Thus, a brief overview on the categories of UCB banks as well as the properties, challenges, and impact of UCB-derived mesenchymal stem cells (MSCs) on the area of cardiovascular research is presented. Taken together, the experience recounted here shows that UCBMSCs are envisioned as attractive therapeutic candidates against human disorders arising and/or progressing with vascular deficit.
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Choi EW, Yun TW, Song JW, Lee M, Yang J, Choi KS. Preventive effects of CTLA4Ig-overexpressing adipose tissue--derived mesenchymal stromal cells in rheumatoid arthritis. Cytotherapy 2014; 17:271-82. [PMID: 25541299 DOI: 10.1016/j.jcyt.2014.10.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2014] [Revised: 10/13/2014] [Accepted: 10/18/2014] [Indexed: 01/29/2023]
Abstract
BACKGROUND AIMS Rheumatoid arthritis is a systemic autoimmune disorder. In this study, we first compared the therapeutic effects of syngeneic and xenogeneic adipose tissue-derived stem cells on a collagen-induced arthritis mouse model. Second, we investigated the synergistic preventive effects of CTLA4Ig and adipose tissue-derived mesenchymal stromal cells (ASCs) as a therapeutic substance. METHODS Arthritis was induced in all groups except for the normal, saline (N) group, using chicken type II collagen (CII). Animals were divided into C (control, saline), H (hASCs), M (mASCs) and N groups (experiment I) and C, H, CT (CTLA4Ig-overexpressing human ASC [CTLA4Ig-hASCs]) and N groups (experiment II), according to transplanted material. Approximately 2 × 10(6) ASCs or 150 μL of saline was intravenously administered on days 24, 27, 30 and 34, and all animals were killed on days 42 to 44 after CII immunization. RESULTS Anti-mouse CII autoantibodies were significantly lower in the H, M and CT groups than in the C group. Cartilage damage severity score and C-telopeptide of type II collagen were significantly lower in the CT group than in the C group. The serum levels of IL-6 were significantly lower in the H, M and CT groups than in the C group. The serum levels of keratinocyte chemoattractant were significantly lower in the CT group than the C group. CONCLUSIONS There were similar effects of ASCs on the decrease of anti-mouse CII autoantibody levels between syngeneic and xenogeneic transplantations, and CTLA4Ig-hASCs showed synergistic preventive effects compared with non-transduced hASCs.
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Affiliation(s)
- Eun Wha Choi
- Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea; School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.
| | - Tae Won Yun
- Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea
| | - Ji Woo Song
- Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea
| | - Minjae Lee
- Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea
| | - Jehoon Yang
- Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea; School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
| | - Kyu-Sil Choi
- Laboratory Animal Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea; School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea
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20
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Polstyanoy AM, Sheina UI, Eremeev AV, Polstyanaya GN, Svetlakov AV. Isolation of germ-cell precursors from human ovary tissue. ACTA ACUST UNITED AC 2014. [DOI: 10.1134/s1990519x14030109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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21
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Abstract
In recent years, a constant growth of knowledge and clinical applications of stem cells have been observed. Mesenchymal stromal cells, also described as mesenchymal stem cells (MSCs) represent a particular cell type for research and therapy because of their ability to differentiate into mesodermal lineage cells. The most investigated source of MSCs is bone marrow (BM). Yet, collection of BM is an invasive procedure associated with significant discomfort to the patient. The procedure results in a relatively low number of these cells, which can decrease with donor's age. Therefore, it seems to be very important to find other sources of mesenchymal stem cells nowadays. A human placenta, which is routinely discarded postpartum, in spite of its natural aging process, is still a rich source of stem cells capable to proliferate and in vitro differentiate in many directions. Besides homing and differentiation in the area of injury, MSCs there elicit strong paracrine effects stimulating the processes of repair. In this review, we focus on the biology, characteristics and potential clinical applications of cells derived from human fetal membranes: amnion and chorion.
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22
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Biazar E, Heidari Keshel S, Rezaei Tavirani M, Jahandideh R. Bone formation in calvarial defects by injectable nanoparticular scaffold loaded with stem cells. Expert Opin Biol Ther 2013; 13:1653-62. [PMID: 24088030 DOI: 10.1517/14712598.2013.840284] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVE Calcium phosphates are one of biomaterials that are used for bone regeneration. In this study, calcium phosphate nanoparticles such as hydroxyapatite (HA)/fluorapatite (FA),with chitosan gel filled with unrestricted somatic stem cells (USSCs) were used for healing calvarial bone in rat model. METHODS The healing effects of these injectable scaffolds, with and without stem cells, in bone regeneration were investigated by computed tomography (CT) analysis and pathology assays after 28 days of grafting. RESULTS The results of CT analysis showed that bone regeneration on the scaffolds, and the amounts of regenerated new bone for USSC scaffold were significantly greater than the scaffold without cell and untreated controls. CONCLUSION Therefore, the combination of scaffold especially with USSC could be considered as a useful method for bone regeneration.
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Affiliation(s)
- Esmaeil Biazar
- Islamic Azad University, Department of Biomaterial Engineering , Tonekabon Branch , Iran +98 1924274415 ; +98 192 427 4411 ;
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23
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Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC, Zhao W. Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab 2013; 33:1322-34. [PMID: 23756689 PMCID: PMC3764389 DOI: 10.1038/jcbfm.2013.91] [Citation(s) in RCA: 103] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Revised: 05/06/2013] [Accepted: 05/08/2013] [Indexed: 12/27/2022]
Abstract
Although ischemic stroke is a major cause of morbidity and mortality, current therapies benefit only a small proportion of patients. Transplantation of mesenchymal stromal cells (MSC, also known as mesenchymal stem cells or multipotent stromal cells) has attracted attention as a regenerative therapy for numerous diseases, including stroke. Mesenchymal stromal cells may aid in reducing the long-term impact of stroke via multiple mechanisms that include induction of angiogenesis, promotion of neurogenesis, prevention of apoptosis, and immunomodulation. In this review, we discuss the clinical rationale of MSC for stroke therapy in the context of their emerging utility in other diseases, and their recent clinical approval for treatment of graft-versus-host disease. An analysis of preclinical studies examining the effects of MSC therapy after ischemic stroke indicates near-universal agreement that MSC have significant favorable effect on stroke recovery, across a range of doses and treatment time windows. These results are interpreted in the context of completed and ongoing human clinical trials, which provide support for MSC as a safe and potentially efficacious therapy for stroke recovery in humans. Finally, we consider principles of brain repair and manufacturing considerations that will be useful for effective translation of MSC from the bench to the bedside for stroke recovery.
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Affiliation(s)
- Mark A Eckert
- Departments of Pharmaceutical Sciences and Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA
| | - Quynh Vu
- Department of Neurology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA
| | - Kate Xie
- Department of Neurology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA
| | - Jingxia Yu
- Departments of Pharmaceutical Sciences and Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA
| | - Wenbin Liao
- Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York, USA
| | - Steven C Cramer
- Departments of Neurology and Anatomy and Neurobiology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA
| | - Weian Zhao
- Departments of Pharmaceutical Sciences and Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA
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Lai RC, Yeo RWY, Tan KH, Lim SK. Mesenchymal stem cell exosome ameliorates reperfusion injury through proteomic complementation. Regen Med 2013; 8:197-209. [DOI: 10.2217/rme.13.4] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Li J, Ezzelarab MB, Cooper DKC. Do mesenchymal stem cells function across species barriers? Relevance for xenotransplantation. Xenotransplantation 2013; 19:273-85. [PMID: 22978461 DOI: 10.1111/xen.12000] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Allogeneic mesenchymal stem (stromal) cells (MSC) are a promising therapy for various pathological conditions. Genetically modified pig MSC have been demonstrated to downregulate the human T-cell response to pig antigens in vitro. Before genetically modified pig MSC can be used clinically, however, evidence needs to be provided to indicate whether they will survive in a human (xenogeneic) host. LITERATURE SEARCH AND RESULTS A literature search through the end of 2011 identified 94 reports of the in vivo cross-species administration of MSC in a variety of experimental models. The majority (n = 89) involved the use of human MSC in various other species, with an occasional study using pig, rat, or guinea-pig MSC. When human MSC were used, they were largely derived from the bone marrow, adipose tissue, or umbilical cord blood. The routes of administration were varied, although almost half of the studies utilized the intravenous route. In 88 experiments (93.6%), there was evidence that the MSC engrafted and functioned across the species barrier, and in only six cases (6.4%) was there evidence of failure to function. Importantly, MSC function was confirmed in several different cross-species models. For example, human MSC functioned in no fewer than seven different recipient species. CONCLUSIONS The data provided by this literature search strengthen the hypothesis that pig MSC will function satisfactorily in a different species, for example, humans. The data also suggest that our own in vitro observations on the efficacy of pig MSC in downregulating the strength of the human T-cell response to pig antigens will likely be reproduced in vivo in pre-clinical large animal models and in clinical trials.
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Affiliation(s)
- Jiang Li
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA
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Tsuno H, Yoshida T, Nogami M, Koike C, Okabe M, Noto Z, Arai N, Noguchi M, Nikaido T. Application of human amniotic mesenchymal cells as an allogeneic transplantation cell source in bone regenerative therapy. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2012. [DOI: 10.1016/j.msec.2012.07.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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Minguell JJ, Allers C, Lasala GP. Mesenchymal stem cells and the treatment of conditions and diseases: the less glittering side of a conspicuous stem cell for basic research. Stem Cells Dev 2012; 22:193-203. [PMID: 23025629 DOI: 10.1089/scd.2012.0417] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Not too long ago, several motivated and forward-looking articles were published describing the cellular and molecular properties of mesenchymal stem cells (MSCs), specially highlighting their potential for self-renewal, commitment, differentiation, and maturation into specific mesoderm-derived lineages. A very influential publication of that period entitled "Mesenchymal stem cells: No longer second class marrow citizens" [1] raised the point of view that "…challenges to harness MSC cell therapy to treat diseases … need to wait for the full comprehension that marrow is a rich source of mesenchyme-derived cells whose potential is still far from fully appreciated." Whether or not the prophecy of Gerson was fulfilled, in the last 8 years it has become evident that infusing MSCs into patients suffering a variety of disorders represents a viable option for medical treatment. Accordingly, a vast number of articles have explored the privileged cellular and molecular features of MSCs prepared from sources other than the canonical, represented by the bone marrow. This review will provide more information neither related to the biological attractiveness of MSCs nor to the success after their clinical use. Rather, we would like to underscore several "critical and tangential" issues, not always discussed in biomedical publications, but relevant to the clinical utilization of bone-marrow-derived MSCs.
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Affiliation(s)
- Jose J Minguell
- TCA Cellular Therapy, 101 Judge Tanner Boulevard, Covington, LA 70433, USA.
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Abstract
Stem cells are emerging as therapeutic candidates in a variety of diseases because of their multipotent capacities. Among these, mesenchymal stem cells (MSCs) derived from bone marrow, umbilical cord blood or adipose tissue, comprise a population of cells that exhibit extensive proliferative potential and retain the ability to differentiate into multiple tissue-specific lineage cells including osteoblasts, chondrocytes, and adipocytes. MSCs have also been shown to enhance neurological recovery, although the therapeutic effects seem to be derived from an indirect paracrine effect rather than direct cell replacement. MSCs secrete neurotrophic factors, promote endogenous neurogenesis and angiogenesis, encourage synaptic connection and remyelination of damaged axons, decrease apoptosis, and regulate inflammation primarily through paracrine actions. Accordingly, MSCs may prevail as a promising cell source for cell-based therapy in neurological diseases.
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Affiliation(s)
- Jung Hwa Seo
- Department of Rehabilitation Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, Korea.
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Lai RC, Yeo RWY, Tan KH, Lim SK. Exosomes for drug delivery - a novel application for the mesenchymal stem cell. Biotechnol Adv 2012; 31:543-51. [PMID: 22959595 DOI: 10.1016/j.biotechadv.2012.08.008] [Citation(s) in RCA: 395] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2012] [Revised: 08/17/2012] [Accepted: 08/17/2012] [Indexed: 02/07/2023]
Abstract
Exosomes are the most extensively characterized class of secreted membrane vesicles that carry proteins and RNAs for intercellular communication. They are increasingly seen as possible alternatives to liposomes as drug delivery vehicles. Like liposomes, they could deliver their cargo across the plasma membrane and provide a barrier against premature transformation and elimination. In addition, these naturally-occurring secreted membrane vesicles are less toxic and better tolerated in the body as evidenced by their ubiquitous presence in biological fluids, and have an intrinsic homing ability. They are also amenable to in vivo and in vitro loading of therapeutic agents, and membrane modifications to enhance tissue-specific homing. Here we propose human mesenchymal stem cells as the ideal cell source of exosomes for drug delivery. Mesenchymal stem cell transplantation for various disease indications has been extensively tested and shown to be safe in numerous clinical trials. These cells are also prolific producers of immunologically inert exosomes. Immortalization of these cells does not compromise the quantity or quality of exosome production, thus enabling infinite and reproducible exosome production from a single cell clone.
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Affiliation(s)
- Ruenn Chai Lai
- Institute of Medical Biology, A*STAR, 8A Biomedical Grove, 138648 Singapore
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Simvastatin mobilizes bone marrow stromal cells migrating to injured areas and promotes functional recovery after spinal cord injury in the rat. Neurosci Lett 2012; 521:136-41. [DOI: 10.1016/j.neulet.2012.05.071] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2012] [Revised: 05/16/2012] [Accepted: 05/29/2012] [Indexed: 01/12/2023]
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Ezzelarab M, Ezzelarab C, Wilhite T, Kumar G, Hara H, Ayares D, Cooper DKC. Genetically-modified pig mesenchymal stromal cells: xenoantigenicity and effect on human T-cell xenoresponses. Xenotransplantation 2011; 18:183-95. [PMID: 21696448 DOI: 10.1111/j.1399-3089.2011.00635.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Mesenchymal stromal cells (MSC) are being investigated as immunomodulatory therapy in the field of transplantation, particularly islet transplantation. While MSC can regenerate across species barriers, the immunoregulatory influence of genetically modified pig MSC (pMSC) on the human and non-human primate T-cell responses has not been studied. METHODS Mesenchymal stromal cells from wild-type (WT), α1,3-galactosyltransferase gene knockout (GTKO) and GTKO pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46) were isolated and tested for differentiation. Antibody binding and T-cell responses to WT and GTKO pMSC in comparison with GTKO pig aortic endothelial cells (pAEC) were investigated. The expression of swine leukocyte antigen (SLA) class II (SLA II) was tested. Costimulatory molecules CD80 and CD86 mRNA levels were measured. Human T-cell proliferation and the production of pro-inflammatory cytokines in response to GTKO and GTKO/CD46 pMSC in comparison with human MSC (hMSC) were evaluated. RESULTS α1,3-galactosyltransferase gene knockout and GTKO/CD46 pMSC isolation and differentiation were achieved in vitro. Binding of human antibodies and T-cell responses were lower to GTKO than those to WT pMSC. Human and baboon (naïve and sensitized) antibody binding were significantly lower to GTKO pMSC than to GTKO pAEC. Before activation, <1% of GTKO pMSC expressed SLA II, compared with 2.5% of GTKO pAEC. After pig interferon-gamma (pIFN-γ) activation, 99% of GTKO pAEC upregulated SLA II expression, compared with 49% of GTKO pMSC. Only 3% of GTKO pMSC expressed CD80 compared with 80% of GTKO pAEC without activation. After pIFN-γ activation, GTKO pAEC upregulated CD86 mRNA level stronger than GTKO pMSC. The human CD4(+) T-cell response to GTKO pMSC was significantly weaker than that to GTKO pAEC, even after pIFN-γ activation. More than 99% of GTKO/CD46 pMSC expressed hCD46. Human peripheral blood mononuclear cells and CD4(+) T-cell responses to GTKO and GTKO/CD46 pMSC were comparable with those to hMSC, and all were significantly lower than to GTKO pAEC. GTKO/CD46 pMSC downregulated human T-cell proliferation as efficiently as hMSC. The level of proinflammatory cytokines IL-2, IFN-γ, TNF-α, and sCD40L correlated with the downregulation of T-cell proliferation by all types of MSC. CONCLUSION Genetically modified pMSC is significantly less immunogenic than WT pMSC. GTKO/CD46 pMSC downregulates the human T-cell responses to pig antigens as efficiently as human MSC, which can be advantageous for therapeutic cell xenotransplantation.
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Affiliation(s)
- Mohamed Ezzelarab
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street,Pittsburgh, PA 15261, USA.
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A natural compound induced cardiogenic differentiation of endogenous MSCs for repair of infarcted heart. Differentiation 2011; 83:1-9. [PMID: 22099171 DOI: 10.1016/j.diff.2011.09.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Revised: 08/11/2011] [Accepted: 09/07/2011] [Indexed: 11/24/2022]
Abstract
An intra-myocardial injection of a cardiogenic factor (cardiogenin) was reported to induce myocardial regeneration of exogenous mesenchymal stem cell (MSCs) origin. In this study, replacement of the dangerous intra-myocardial injection with a safe method and whether the endogenous MSCs contribute to the cardiogenin-mediated myocardial regeneration were investigated. Bone marrow transplantation with labeled MSCs was performed in rats, which were subsequently subject to a permanent ligation of left anterior descending coronary artery one week after the transplantation. The rats were then treated with the cardiogenin through oral administration for 2 weeks. We not only demonstrated the substantial therapeutic effects of cardiogenin on myocardial infarction through an oral administration, but also provided direct evidences that the bone marrow derived endogenous MSCs are the major cellular source of the regenerating myocardium. Preliminary mechanistic studies suggested that miR-9 and its target E-cadherin may be required for intercalated disc formation.
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Abstract
The hematopoietic microenvironment, and in particular the hematopoietic stromal cell element, are intimately involved in megakaryocyte development. The process of megakaryocytopoiesis occurs within a complex bone marrow microenvironment where adhesive interactions, chemokines, as well as cytokines play a pivotal role. Here we review the effect of stromal cells and cytokines on megakaryocytopoiesis with the aim of exploring new therapeutic strategies for platelet recovery after hematopoietic stem cell transplantation (HSCT).
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Affiliation(s)
- Yimei Feng
- Department of Hematology, Second Affiliated Hospital, Third Military Medical University, Chongqing, China
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34
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Wu ZX, Yang XZ, Cai JQ, Liao LM, Yang L, Lin YN, Tan JM. Digital subtraction angiography and computed tomography angiography of predominant artery feeding pancreatic body and tail. Diabetes Technol Ther 2011; 13:537-41. [PMID: 21406019 DOI: 10.1089/dia.2010.0173] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Recently a considerable number of promising clinical trials have been designed to perform infusion of stem cells by pancreatic arterial intervention to improve the endocrine function of the pancreas for better diabetes control. It is necessary to investigate the pancreatic body and tail (PBT) arterial system for human islets located mostly in the PBT and identify the predominant artery or arteries. However, the arterial system in the PBT is complicated and variable. In this study we comprehensively investigated the anatomical characteristics of arteries feeding the PBT. RESEARCH DESIGN AND METHODS One hundred two patients with diabetes underwent 64-slice computed tomography angiography (CTA) and digital subtraction angiography (DSA). The target artery was catheterized, and DSA was performed to show the PBT. All images were documented for later analysis. RESULTS DSA demonstrated that the feeding arteries for the PBT included the dorsal pancreatic artery (DPA) alone (n = 51 [50%]), combined DPA and great pancreatic artery (GPA) (n = 22 [21.6%]), GPA alone (n = 16 [15.7%]), and transverse pancreatic artery (TPA) (n = 11 [10.8%]). DPA was observed to originate from the initial segment of the splenic artery (n = 34 [46.6%]), common hepatic artery (n = 17 [23.3%]), or superior mesenteric artery (n = 14 [19.2%]). The GPA was mostly from the middle (n = 36 [94.7%]), and only two were found to originate from the initial segment of the splenic artery. The TPA (n = 11) was from either the pancreatoduodenal artery (n = 5 [54.5%]) or the gastroduodenal artery (n = 4 [36.4%]). In most case, the predominant artery of the PBT (95.1%, 97 of 102) could be revealed by 64-slice CTA. CONCLUSIONS The origins and identities of the predominant artery in the PBT are variable. DSA is superior to CTA for preoperative imaging in arterial intervention therapy.
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Affiliation(s)
- Zhi-xian Wu
- Transplant Center, Fuzhou Medical College, Fuzhou General Hospital, Second Military Medical University, Fuzhou, China
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35
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Deak E, Seifried E, Henschler R. Homing pathways of mesenchymal stromal cells (MSCs) and their role in clinical applications. Int Rev Immunol 2011; 29:514-29. [PMID: 20839913 DOI: 10.3109/08830185.2010.498931] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Mesenchymal stromal cells (MSCs) have come into focus for an increasing number of cellular therapies. Since most clinical protocols use intravenous application of MSCs, it has become important to understand their trafficking in the bloodstream. Moreover, since relatively little is known where the transplanted MSCs might locate, a better understanding of involved homing mechanisms will likely shed light on how MSCs exert their therapeutic effects. This review focuses on the current knowledge of homing pathways of transplanted MSCs. We describe regulatory signalling molecules and receptors involved. An outlook is given on significance of these findings for the future use of MSCs as a cellular therapeutic.
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Affiliation(s)
- Erika Deak
- Stem Cell Biology Group, DRK Institute of Transfusion Medicine and Immune Hematology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
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36
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Umbilical cord blood-derived mesenchymal cell fate after mouse umbilical cord blood transplantation. Transplantation 2010; 90:1037-9. [PMID: 21037462 DOI: 10.1097/tp.0b013e3181f674f6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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37
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Bieback K, Brinkmann I. Mesenchymal stromal cells from human perinatal tissues: From biology to cell therapy. World J Stem Cells 2010; 2:81-92. [PMID: 21607124 PMCID: PMC3097927 DOI: 10.4252/wjsc.v2.i4.81] [Citation(s) in RCA: 84] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2010] [Revised: 08/11/2010] [Accepted: 08/16/2010] [Indexed: 02/06/2023] Open
Abstract
Cell-based regenerative medicine is of growing interest in biomedical research. The role of stem cells in this context is under intense scrutiny and may help to define principles of organ regeneration and develop innovative therapeutics for organ failure. Utilizing stem and progenitor cells for organ replacement has been conducted for many years when performing hematopoietic stem cell transplantation. Since the first successful transplantation of umbilical cord blood to treat hematological malignancies, non-hematopoietic stem and progenitor cell populations have recently been identified within umbilical cord blood and other perinatal and fetal tissues. A cell population entitled mesenchymal stromal cells (MSCs) emerged as one of the most intensely studied as it subsumes a variety of capacities: MSCs can differentiate into various subtypes of the mesodermal lineage, they secrete a large array of trophic factors suitable of recruiting endogenous repair processes and they are immunomodulatory.Focusing on perinatal tissues to isolate MSCs, we will discuss some of the challenges associated with these cell types concentrating on concepts of isolation and expansion, the comparison with cells derived from other tissue sources, regarding phenotype and differentiation capacity and finally their therapeutic potential.
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Affiliation(s)
- Karen Bieback
- Karen Bieback, Irena Brinkmann, Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, DRK-Blutspendedienst Baden-Württemberg - Hessen gGmbH, Ludolf-Krehl-Str. 13-17, D-68167 Mannheim, Germany
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38
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Wilson T, Stark C, Holmbom J, Rosling A, Kuusilehto A, Tirri T, Penttinen R, Ekholm E. Fate of bone marrow-derived stromal cells after intraperitoneal infusion or implantation into femoral bone defects in the host animal. J Tissue Eng 2010; 2010:345806. [PMID: 21350643 PMCID: PMC3042670 DOI: 10.4061/2010/345806] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2009] [Revised: 03/26/2010] [Accepted: 06/02/2010] [Indexed: 01/16/2023] Open
Abstract
The fate of intraperitoneally injected or implanted male rat bone marrow-derived stromal cells inside female sibling host animals was traced using Y-chromosome-sensitive PCR. When injected intraperitoneally, Y-chromosome-positive cells were found in all studied organs: heart muscle, lung, thymus, liver, spleen, kidney, skin, and femoral bone marrow with a few exceptions regardless of whether they had gone through osteogenic differentiation or not. In the implant experiments, expanded donor cells were seeded on poly(lactide-co-glycolide) scaffolds and grown under three different conditions (no additives, in osteogenic media for one or two weeks) prior to implantation into corticomedullar femoral defects. Although the impact of osteogenic in vitro cell differentiation on cell migration was more obvious in the implantation experiments than in the intraperitoneal experiments, the donor cells stay alive when injected intraperitoneally or grown in an implant and migrate inside the host. However, when the implants contained bioactive glass, no signs of Y-chromosomal DNA were observed in all studied organs including the implants indicating that the cells had been eliminated.
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Affiliation(s)
- Timothy Wilson
- Department of Medical Biochemistry and Genetics, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
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39
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Liu G, Li Y, Sun J, Zhou H, Zhang W, Cui L, Cao Y. In vitro and in vivo evaluation of osteogenesis of human umbilical cord blood-derived mesenchymal stem cells on partially demineralized bone matrix. Tissue Eng Part A 2010; 16:971-82. [PMID: 19839720 DOI: 10.1089/ten.tea.2009.0516] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
The osteogenic differentiation potential of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) has been documented previously, and partially demineralized bone matrix (pDBM) represents a promising candidate for bone tissue engineering scaffolds. In this study, pDBM scaffolds derived from porcine cancellous bone were evaluated for their ability to support human UCB-MSCs osteogenic differentiation in vitro and bone-forming capacity in vivo to assess the potential use of UCB-MSCs in bone tissue engineering applications. MSCs were isolated from full-term human UCB and expanded, and their cell surface antigen markers and multilineage capability to differentiate into osteoblasts, chondrocytes, and adipocytes were analyzed. The in vitro proliferation and osteogenic differentiation of UCB-MSCs loaded onto the three-dimensional pDBM scaffolds were determined. Critical-sized full-thickness circular defects (5 mm in diameter) created bilaterally in the parietal bones of athymic rats were treated with one of the following: osteogenically induced UCB-MSC/pDBM composites (Group A, n = 8), noninduced UCB-MSC/pDBM composites (Group B, n = 8), pDBM alone (Group C, n = 8), or left untreated (Group D, n = 8). Microcomputed tomography analysis showed that new bone was formed in Group A at 6 weeks postimplantation, and greater bone volume and density were found after 12 weeks. In other groups, new bone formation was not evident after 6 weeks, and no bone union was found at 12 weeks. Histological examination revealed that the defect was repaired by tissue-engineered bone in Group A at 12 weeks, and fibrous union was observed in Groups B, C, and D. These results demonstrate that pDBM can support osteogenic differentiation of human UCB-MSCs in vitro and in vivo, and UCB-MSCs may serve as an alternative cell source for bone tissue engineering and regeneration.
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Affiliation(s)
- Guangpeng Liu
- The Key Laboratory of Tissue Engineering, Shanghai 9th People's Hospital, Shanghai JiaoTong Universtiy School of Medicine, Shanghai, China
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40
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Lu X, Alshemali S, de Wynter EA, Dickinson AM. Mesenchymal stem cells from CD34−human umbilical cord blood. Transfus Med 2010; 20:178-84. [DOI: 10.1111/j.1365-3148.2009.00981.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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41
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Bertoldi S, Farè S, Denegri M, Rossi D, Haugen HJ, Parolini O, Tanzi MC. Ability of polyurethane foams to support placenta-derived cell adhesion and osteogenic differentiation: preliminary results. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2010; 21:1005-1011. [PMID: 20012164 DOI: 10.1007/s10856-009-3953-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2009] [Accepted: 11/25/2009] [Indexed: 05/28/2023]
Abstract
In bone tissue reconstruction, the use of engineered constructs created by mesenchymal stem cells (MSCs) that differentiate and proliferate into 3D porous scaffolds is an appealing alternative to clinical therapies. Human placenta represents a possible source of MSCs, as it is readily available without invasive procedures and because of the phenotypic plasticity of many of the cell types isolated from this tissue. The scaffold considered in this work is a slowly degradable polyurethane foam (EF PU foam), synthesized and characterized for morphology and in vitro interaction with chorion mesenchymal cells (CMCs). These cells were isolated from human term placenta and cultured onto the EF PU foam using two different culture media (EMEM and NH osteogenic differentiation medium). Synthesized EF PU foam showed homogeneous pore size and distribution, with 89% open porosity. In vitro tests showed CMCs scaffold colonization, as confirmed by Scanning Electron Microscopy (SEM) observations and hematoxylin-eosin staining. Alizarin Red staining revealed the presence of a small amount of calcium deposition for the samples treated with the osteogenic differentiation medium. Therefore, the proposed EF PU foam appears to stimulate cell adhesion in vitro, sustaining CMCs growth and differentiation into the osteogenic lineage.
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Affiliation(s)
- S Bertoldi
- Biomaterials Laboratory, Bioengineering Department, Politecnico di Milano, P.zza Leonardo da Vinci 32, 20133, Milan, Italy.
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42
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Caen J. Les cellules souches du cordon et du placenta : de la recherche aux applications thérapeutiques. BULLETIN DE L ACADEMIE NATIONALE DE MEDECINE 2010. [DOI: 10.1016/s0001-4079(19)32346-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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43
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Ding W, Nowakowski GS, Knox TR, Boysen JC, Maas ML, Schwager SM, Wu W, Wellik LE, Dietz AB, Ghosh AK, Secreto CR, Medina KL, Shanafelt TD, Zent CS, Call TG, Kay NE. Bi-directional activation between mesenchymal stem cells and CLL B-cells: implication for CLL disease progression. Br J Haematol 2009; 147:471-83. [PMID: 19751240 DOI: 10.1111/j.1365-2141.2009.07868.x] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
It was hypothesized that contact between chronic lymphocytic leukaemia (CLL) B-cells and marrow stromal cells impact both cell types. To test this hypothesis, we utilized a long-term primary culture system from bone biopsies that reliably generates a mesenchymal stem cell (MSC). Co-culture of MSC with CLL B-cells protected the latter from both spontaneous apoptosis and drug-induced apoptosis. The CD38 expression in previously CD38 positive CLL B-cells was up-regulated with MSC co-culture. Upregulation of CD71, CD25, CD69 and CD70 in CLL B-cells was found in the co-culture. CD71 upregulation was more significantly associated with high-risk CLL, implicating CD71 regulation in the microenvironment predicting disease progression. In MSC, rapid ERK and AKT phosphorylation (within 30 min) were detected when CLL B-cells and MSC were separated by transwell; indicating that activation of MSC was mediated by soluble factors. These findings support a bi-directional activation between bone marrow stromal cells and CLL B-cells.
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Affiliation(s)
- Wei Ding
- Division of Hematology/Oncology, Mayo Clinic, Rochester, MN 55905, USA
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44
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Kuo TK, Ho JH, Lee OK. Mesenchymal Stem Cell Therapy for Nonmusculoskeletal Diseases: Emerging Applications. Cell Transplant 2009; 18:1013-28. [DOI: 10.3727/096368909x471206] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Mesenchymal stem cells are stem/progenitor cells originated from the mesoderm and can different into multiple cell types of the musculoskeletal system. The vast differentiation potential and the relative ease for culture expansion have established mesenchymal stem cells as the building blocks in cell therapy and tissue engineering applications for a variety of musculoskeletal diseases, including repair of fractures and bone defects, cartilage regeneration, treatment of osteonecrosis of the femoral head, and correction of genetic diseases such as osteogenesis imperfect. However, research in the past decade has revealed differentiation potentials of mesenchymal stem cells beyond lineages of the mesoderm, suggesting broader applications than originally perceived. In this article, we review the recent developments in mesenchymal stem cell research with respect to their emerging properties and applications in nonmusculoskeletal diseases.
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Affiliation(s)
- Tom K. Kuo
- Stem Cell Research Center, National Yang-Ming University, Taiwan
| | - Jennifer H. Ho
- Graduate Institute of Clinical Medicine, Taipei Medical University, Taiwan
- Department of Ophthalmology, Taipei Medical University-Wan Fang Hospital, Taiwan
| | - Oscar K. Lee
- Stem Cell Research Center, National Yang-Ming University, Taiwan
- Institute of Clinical Medicine, National Yang-Ming University, Taiwan
- Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan
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45
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Yu SJ, Soncini M, Kaneko Y, Hess DC, Parolini O, Borlongan CV. Amnion: a potent graft source for cell therapy in stroke. Cell Transplant 2009; 18:111-8. [PMID: 19499700 DOI: 10.3727/096368909788341243] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.
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Affiliation(s)
- Seong Jin Yu
- Department of Neurology, Medical College of Georgia, Augusta, GA, USA
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46
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Kidd S, Spaeth E, Klopp A, Andreeff M, Hall B, Marini FC. The (in) auspicious role of mesenchymal stromal cells in cancer: be it friend or foe. Cytotherapy 2009; 10:657-67. [PMID: 18985472 DOI: 10.1080/14653240802486517] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Recent progress in the research of mesenchymal stromal cells/multipotent stromal cells (MSC) has revealed numerous beneficial innate characteristics, suggesting potential value in an array of cellular therapies. MSC are easily isolated from bone marrow (BM), fat and other tissues, and are readily propagated in vitro. Transplanted/injected MSC have been shown to migrate to a variety of organs and tissues; however, sites of inflammation and pathology elicit enhanced MSC homing for tissue remodeling and repair. Tumors utilize many of the same inflammatory mediators uncovered in wound healing and likewise provide a site for preferential MSC homing. Although incorporation into the tumor microenvironment is apparent, the role of recruited MSC in the tumor microenvironment remains unclear. Some published studies have shown enhancement of tumor growth and development, perhaps through immunomodulatory and pro-angiogenic properties, while others have shown no apparent effect or have demonstrated inhibition of tumor growth and extended survival. This controversy remains at the forefront as clinical applications of MSC commence in anti-tumor therapies as well as as adjuncts to stem cell transplantation and in ameliorating graft-versus-host disease. Careful analysis of past studies and thoughtful design of future experiments will help to resolve the discrepancies in the field and lead to clinical utility of MSC in disease treatment. This review highlights the current theories of the role of MSC in tumors and explores current controversies.
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Affiliation(s)
- S Kidd
- Section of Experimental Hematology and Therapy, Department of Stem Cell Transplant and Cellular Therapy, UT-MD Anderson Cancer Center, Houston, Texas, USA
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47
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Jäger M, Zilkens C, Bittersohl B, Krauspe R. Cord blood--an alternative source for bone regeneration. Stem Cell Rev Rep 2009; 5:266-77. [PMID: 19652969 DOI: 10.1007/s12015-009-9083-z] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2009] [Accepted: 07/20/2009] [Indexed: 12/12/2022]
Abstract
Bone regeneration is one of the best investigated pathways in mesenchymal stromal cell (MSC) biology. Therefore strong efforts have been made to introduce tissue engineering and cell therapeutics as an alternative treatment option for patients with bone defects. This review of the literature gives an overview of MSC biology aiming for clinical application including advantages but also specific challenges and problems which are associated with cord blood derived stromal cell (CB-MSC) as a source for bone regeneration. The use of postnatal CB-MSC is ethically uncomplicated and requires no invasive harvesting procedure. Moreover, most data document a high osteogenic potential of CB-MCS and also low immunoreactivity compared with other MSC types. The expression profile of CB-MSC during osteogenic differentiation shows similarities to that of other MSC types. Within the umbilical cord different MSC types have been characterized which are potent to differentiate into osteoblasts. In contrast to a large number of in vitro investigations there are only few in vivo studies available so far.
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Affiliation(s)
- Marcus Jäger
- Department of Orthopaedics, Heinrich-Heine University Medical School, Moorenstrasse 5, 40225, Düsseldorf, Germany.
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48
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Abstract
Mesenchymal stem cells (MSCs) are the stromal component of bone marrow (BM) and, at the moment, the most promising prospect for tissue regeneration and repair. MSCs are easily obtained from BM, have the potential to differentiate into several cell types, and show immunomodulatory properties. The use of MSCs for cell therapies relies on the capacity of these cells to home and engraft long term into the appropriate target tissue. During the past decade, MSC homing capacity to BM and other organs has been reported. Although the mechanisms by which MSCs are recruited to tissues and cross the endothelial cell layer are not yet fully understood, it is probable that chemokines and their receptors are involved, as they are important factors known to control cell migration. The CXCR4-CXCL12 and CX3CR1-CX3CL1 axes, for instance, drive the crosstalk between MSCs and pancreatic islets.
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49
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Pal R, Hanwate M, Jan M, Totey S. Phenotypic and functional comparison of optimum culture conditions for upscaling of bone marrow-derived mesenchymal stem cells. J Tissue Eng Regen Med 2009; 3:163-74. [PMID: 19229888 DOI: 10.1002/term.143] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Human adult bone marrow-derived mesenchymal stem cells (MSCs) are a promising tool in the newly emerging avenue of regenerative medicine. MSCs have already been translated from basic research to clinical transplantation research. However, there is still a lack of consensus on the ideal method of culturing MSCs. Here we have compared different culture conditions of human MSCs with an attempt to preserve their characteristics and multi-lineage differentiation potential. We compare the different basal culture media DMEM-F12, DMEM-high glucose (DMEM-HG), DMEM-low glucose (DMEM-LG), knock-out DMEM (DMEM-KO) and Mesencult on the proliferation rate, surface markers and differentiation potentials of MSCs. At every fifth passage until the 25th passage, the differentiation potential and the presence of a panel of surface markers was observed, using flow cytometry. We also compared the characteristics of human MSCs when cultured in reduced concentrations of fetal bovine serum (FBS), knockout serum replacement (KO-SR) and human plasma. Data indicate that the presence of serum is essential to sustain and propagate MSCs cultures. The choice of basal medium is equally important so as to preserve their characteristics and multipotent properties even after prolonged culture in vitro. With MSCs emerging as a popular tool for regenerative therapies in incurable diseases, it is essential to be able to obtain a large number of MSCs that continue to preserve their characteristics following passaging. The data reveal the optimum basal medium for prolonged culture of MSCs while retaining their ability to differentiate and hence this may be used for up-scaling to provide sufficient numbers for transplantation.
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Affiliation(s)
- Rakhi Pal
- Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, India
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50
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Barachini S, Trombi L, Danti S, D'Alessandro D, Battolla B, Legitimo A, Nesti C, Mucci I, D'Acunto M, Cascone MG, Lazzeri L, Mattii L, Consolini R, Petrini M. Morpho-functional characterization of human mesenchymal stem cells from umbilical cord blood for potential uses in regenerative medicine. Stem Cells Dev 2009; 18:293-305. [PMID: 18444788 DOI: 10.1089/scd.2008.0017] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Mesenchymal stem cells (MSCs) represent a promising source of progenitor cells having the potential to repair and to regenerate diseased or damaged skeletal tissues. Bone marrow (BM) has been the first source reported to contain MSCs. However, BM-derived cells are not always acceptable, due to the highly invasive drawing and the decline in MSC number and differentiative capability with increasing age. Human umbilical cord blood (UCB), obtainable by donation with a noninvasive method, has been introduced as an alternative source of MSCs. Here human UCB-derived MSCs isolation and morpho-functional characterization are reported. Human UCB-derived mononuclear cells, obtained by negative immunoselection, exhibited either an osteoclast-like or a mesenchymal-like phenotype. However, we were able to obtain homogeneous populations of MSCs that displayed a fibroblast-like morphology, expressed mesenchym-related antigens and showed differentiative capacities along osteoblastic and early chondroblastic lineages. Furthermore, this study is one among a few papers investigating human UCB-derived MSC growth and differentiation on three-dimensional scaffolds focusing on their potential applications in regenerative medicine and tissue engineering. UCB-derived MSCs were proved to grow on biodegradable microfiber meshes; additionally, they were able to differentiate toward mature osteoblasts when cultured inside human plasma clots, suggesting their potential application in orthopedic surgery.
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Affiliation(s)
- Serena Barachini
- RRMR/CUCCS, Regional Network of Regenerative Medicine/Center for the Clinical Use of Stem Cells, University of Pisa, Pisa, Italy.
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