Huang Sha, Wu Yan, Gao Dongyun, Fu Xiaobing
Key Laboratory of Wound Repair and Regeneration of PLA, The First Affiliated Hospital, General Hospital of PLA, Trauma Center of Postgraduate Medical College, Beijing, Peoples Republic of China; Wound Healing and Cell Biology Laboratory, Institute of Basic Medical Sciences, General Hospital of PLA, Beijing, Peoples Republic of China; Hainan Branch of the Chinese PLA General Hospital, Sanya, Hainan Province, Peoples Republic of China.
Key Laboratory of Wound Repair and Regeneration of PLA, The First Affiliated Hospital, General Hospital of PLA, Trauma Center of Postgraduate Medical College, Beijing, Peoples Republic of China; Heilongjiang Key Laboratory of Anti-Fibrosis Biotherapy, Mudanjiang Medical College, Mudanjiang, Peoples Republic of China.
Cytotherapy. 2015 Jul;17(7):922-31. doi: 10.1016/j.jcyt.2015.03.690. Epub 2015 May 1.
Accumulating evidence suggests that mesenchymal stromal cells (MSCs) participate in wound healing to favor tissue regeneration and inhibit fibrotic tissue formation. However, the evidence of MSCs to suppress cutaneous scar is extremely rare, and the mechanism remains unidentified. This study aimed to demonstrate whether MSCs-as the result of their paracrine actions on damaged tissues-would accelerate wound healing and prevent cutaneous fibrosis.
For efficient delivery of MSCs to skin wounds, microspheres were used to maintain MSC potency. Whether MSCs can accelerate wound healing and alleviate cutaneous fibrosis through paracrine action was investigated with the use of a Transwell co-culture system in vitro and a murine model in vivo.
MSCs cultured on gelatin microspheres fully retained their cell surface marker expression profile, proliferation, differentiation and paracrine potential. Co-cultures of MSCs and fibroblasts indicated that the benefits of MSCs on suppressing fibroblast proliferation and its fibrotic behavior induced by inflammatory cytokines probably were caused by paracrine actions. Importantly, microspheres successfully delivered MSCs into wound margins and significantly accelerated wound healing and concomitantly reduced the fibrotic activities of cells within the wounds and excessive accumulation of extracellular matrix as well as the transforming growth factor-β1/transforming growth factor-β3 ratio.
This study provides insight into what we believe to be a previously undescribed, multifaceted role of MSC-released protein in reducing cutaneous fibrotic formation. Paracrine action of MSCs delivered by microspheres may thus qualify as a promising strategy to enhance tissue repair and to prevent excessive fibrosis during cutaneous wound healing.
越来越多的证据表明，间充质基质细胞（MSC）参与伤口愈合，促进组织再生并抑制纤维化组织形成。然而，MSC抑制皮肤瘢痕的证据极为罕见，其机制仍不明晰。本研究旨在证明MSC是否因其对受损组织的旁分泌作用而加速伤口愈合并预防皮肤纤维化。
为了将MSC有效地递送至皮肤伤口，使用微球来维持MSC的效能。利用体外Transwell共培养系统和体内小鼠模型，研究MSC是否能通过旁分泌作用加速伤口愈合并减轻皮肤纤维化。
在明胶微球上培养的MSC完全保留了其细胞表面标志物表达谱、增殖、分化及旁分泌潜能。MSC与成纤维细胞的共培养表明，MSC对抑制成纤维细胞增殖及其由炎性细胞因子诱导的纤维化行为的益处可能是由旁分泌作用引起的。重要的是，微球成功地将MSC递送至伤口边缘，显著加速了伤口愈合，并同时降低了伤口内细胞的纤维化活性、细胞外基质的过度积聚以及转化生长因子-β1/转化生长因子-β3的比值。
本研究深入探讨了我们认为MSC释放的蛋白质在减少皮肤纤维化形成方面以前未被描述的多方面作用。因此，微球递送的MSC的旁分泌作用可能成为一种有前景的策略，以增强组织修复并预防皮肤伤口愈合过程中的过度纤维化。
