Human Wharton's Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells

Autor: Aline Yen Ling Wang, Chin-Ming Lee, Chia-Hsien Lin, Sing-Ying Hsieh, Charles Yuen Yung Loh, Hsin-Hsin Shen, Ing-Kae Wang
Rok vydání: 2020
Předmět:
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 17
International Journal of Molecular Sciences, Vol 21, Iss 6310, p 6310 (2020)
ISSN: 1422-0067
Popis: The acceleration of peripheral nerve regeneration is crucial for functional nerve recovery. Our previous study demonstrated that human Wharton&rsquo
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.
Databáze: OpenAIRE