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
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.
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
Fig.1
Fig.2
Fig.3
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
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
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62
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75
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76
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77
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78
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79
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