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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (2) : 138-151    https://doi.org/10.1007/s11684-018-0627-y
REVIEW
Mesenchymal stem cells and immune disorders: from basic science to clinical transition
Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao()
Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine, Peking Union Medical College; Peking Union Medical College Hospital; Center of Excellence in Tissue Engineering, Chinese Academy of Medical Sciences, Beijing 100005, China
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Abstract

As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

Keywords mesenchymal stem cell      clinical transition      immune disorders     
Corresponding Author(s): Robert Chunhua Zhao   
Just Accepted Date: 19 June 2018   Online First Date: 31 July 2018    Issue Date: 28 March 2019
 Cite this article:   
Shihua Wang,Rongjia Zhu,Hongling Li, et al. Mesenchymal stem cells and immune disorders: from basic science to clinical transition[J]. Front. Med., 2019, 13(2): 138-151.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0627-y
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I2/138
No. Basic characteristics of MSCs
1 Plastic-adherent
2 CD105, CD73, and CD90 positive; CD45, CD34, CD14 CD11b, CD79a, CD19, and HLA class II negative
3 Osteogenic, chondrogenic, and adipogenic differentiation capacities
Tab.1  Basic characteristics of MSCs
Fig.1  Concept of the MSC system.
Fig.2  “Yin and Yang” balance of MSC regulation.
Fig.3  Analysis of clinical trials of MSC on immune-related diseases (in October 17, 2016, n = 125). (A) clinical trials classified by disease types and different systems; (B) numbers of newly created clinical trials of MSC on immune-related disorders over these years; (C) clinical trials of MSCs classified by donors; (D) clinical trials of MSCs classified by tissue sources; and (E) clinical trials of MSCs classified by phases.
Disease Number Dose Source Route Result References
RA 4 1 × 106/kg Allo-BM iv Negative [92]
RA 136 4 × 107 total Allo-UC iv Remission [93]
Juvenile RA 10 4 × 107 total Allo-UC iv Effective [94]
Aplastic anemia 4 2.7 × 106/kg Allo-BM iv, 2–5 times Unimproved [104]
Dermatomyositis 10 1 × 106/kg Allo-BM/UC iv Effective [102]
Ankylosing spondylitis 31 1 × 106/kg Allo-BM iv, 4 times Improved [101]
Systemic sclerosis 12 3.76 × 106 each finger Allo-AT Subcutaneous injection Improved [96]
Tab.2  Clinical trials/pilot studies of MSCs for other immune-related diseases within five years
References Weng et al. (2012) [113] Zhao et al. (2015) [66] Wang et al. (2014) [114] Wang et al. (2013) [94] Gu et al. (2014) [115] Wu et al. (2013) [116] Wang et al. (2013) [117] Qiao et al. (2014) [118] Li et al. (2014) [119] Wang et al. (2014) [101] Zheng et al. (2014) [120] Wang et al. (2013) [121]
No. of patients Treatment (n = 22) Control (n = 19); treatment (n = 28) Treatment (n = 10) Treatment (n = 7) Treatment (n = 81) Control (n = 12); treatment (n = 8) Treatment (n = 52) Treatment (n = 8) Control (n = 10); treatment (n = 13) Treatment (n = 31) Control (n = 6); treatment (n = 6) Control (n = 20); treatment (n = 20)
Follow-up period 3 months 1 year 12 months 48 weeks 1 year 16.5 months (range, 8–27 months) 18 months 2 years follow-up 12 months 20 weeks 28 days follow-up 6 months
Disease Refractory dry eye secondary to cGVHD Refractory aGVHD UDCA-resistant primary biliary cirrhosis Primary biliary cirrhosis Refractory lupus nephritis Delayed hematopoietic reconstitution after cord blood transplantation Cerebral palsy Stroke Multiple sclerosis Active ankylosing spondylitis Acute respiratory distress syndrome Sequelae of traumatic brain injury
Outcome 54.55% of the patients exhibited improved clinical symptoms after MSC treatment 75% of the patients exhibited improved clinical symptoms after MSC treatment, which was derived from the bone marrow of a third-party donor The life quality of the patients was improved for 12 months after BM-MSC treatment Symptoms (e.g., fatigue and pruritus) were significantly improved after UC-MSC transplantation Renal remission was observed in active LN patients after allogeneic MSC treatment Neutrophil and platelet engraftment time was obviously short in patients after UC-MSC treatment GMFM-88 and GMFM-66 scores were increased after MSC treatment Neurological functions and daily living abilities were improved after MSC treatment Overall symptoms were improved in patients after UC-MSC treatment The average total inflammation extent was decreased in patients after MSC treatment Clinical effect was weak after allogeneic adipose-derived MSCs transplantation Neurological function and self-care were improved in patients after UC-MSC transplantation
Tab.3  Examples of clinical trials performed in China
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