期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 17, 页码 -出版社
MDPI
DOI: 10.3390/ijms21176310
关键词
Wharton's jelly; mesenchymal stem cells; sciatic nerve; transection; neurotmesis; peripheral nerve; regeneration; regulatory T cells; Treg
资金
- Chang Gung Medical Foundation, Chang Gung Memorial Hospital, Taiwan [CMRPG1H0081, CMRPG1H0082, CMRPG1H0083]
- Ministry of Science and Technology, Taiwan [MOST 108-2314-B-182A-009-, MOST 109-2314-B-182A-056 -MY3]
The acceleration of peripheral nerve regeneration is crucial for functional nerve recovery. Our previous study demonstrated that human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSC) promote sciatic nerve recovery and regeneration via the direct upregulation and release of neurotrophic factors. However, the immunomodulatory role of hWJ-MSC in sciatic nerve recovery remains unclear. The effects of hWJ-MSC on innate immunity, represented by macrophages, natural killer cells, and dendritic cells, as well as on adaptive immunity, represented by CD4(+)T, CD8(+)T, B, and regulatory T cells (Tregs), were examined using flow cytometry. Interestingly, a significantly increased level of Tregs was detected in blood, lymph nodes (LNs), and nerve-infiltrating cells on POD7, 15, 21, and 35. Anti-inflammatory cytokines, such as IL-4 and IL-10, were significantly upregulated in the LNs and nerves of hWJ-MSC-treated mice. Treg depletion neutralized the improved effects of hWJ-MSC on sciatic nerve recovery. In contrast, Treg administration promoted the functional recovery of five-toe spread and gait stance. hWJ-MSC also expressed high levels of the anti-inflammatory cytokines TGF-beta and IL-35. This study indicated that hWJ-MSC induce Treg development to modulate the balance between pro- and anti-inflammation at the injured sciatic nerve by secreting higher levels of anti-inflammatory cytokines.
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