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人脐带华通氏胶间充质干细胞的可塑性增强无瘢痕皮肤伤口愈合并促进毛发生长。

Human Wharton's Jelly Mesenchymal Stem Cells plasticity augments scar-free skin wound healing with hair growth.

作者信息

Sabapathy Vikram, Sundaram Balasubramanian, V M Sreelakshmi, Mankuzhy Pratheesh, Kumar Sanjay

机构信息

Center for Stem Cell Research (CSCR), Christian Medical College (CMC), Bagayam, Vellore, Tamil Nadu, India.

School of Bioscience and Technology, VIT University, Vellore, Tamil Nadu, India.

出版信息

PLoS One. 2014 Apr 15;9(4):e93726. doi: 10.1371/journal.pone.0093726. eCollection 2014.

Abstract

Human mesenchymal stem cells (MSCs) are a promising candidate for cell-based transplantation and regenerative medicine therapies. Thus in the present study Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) have been derived from extra embryonic umbilical cord matrix following removal of both arteries and vein. Also, to overcome the clinical limitations posed by fetal bovine serum (FBS) supplementation because of xenogeneic origin of FBS, usual FBS cell culture supplement has been replaced with human platelet lysate (HPL). Apart from general characteristic features of bone marrow-derived MSCs, wharton jelly-derived MSCs have the ability to maintain phenotypic attributes, cell growth kinetics, cell cycle pattern, in vitro multilineage differentiation plasticity, apoptotic pattern, normal karyotype-like intrinsic mesenchymal stem cell properties in long-term in vitro cultures. Moreover, the WJ-MSCs exhibited the in vitro multilineage differentiation capacity by giving rise to differentiated cells of not only mesodermal lineage but also to the cells of ectodermal and endodermal lineage. Also, WJ-MSC did not present any aberrant cell state upon in vivo transplantation in SCID mice and in vitro soft agar assays. The immunomodulatory potential assessed by gene expression levels of immunomodulatory factors upon exposure to inflammatory cytokines in the fetal WJ-MSCs was relatively higher compared to adult bone marrow-derived MSCs. WJ-MSCs seeded on decellularized amniotic membrane scaffold transplantation on the skin injury of SCID mice model demonstrates that combination of WJ-MSCs and decellularized amniotic membrane scaffold exhibited significantly better wound-healing capabilities, having reduced scar formation with hair growth and improved biomechanical properties of regenerated skin compared to WJ-MSCs alone. Further, our experimental data indicate that indocyanin green (ICG) at optimal concentration can be resourcefully used for labeling of stem cells and in vivo tracking by near infrared fluorescence non-invasive live cell imaging of labelled transplanted cells, thus proving its utility for therapeutic applications.

摘要

人间充质干细胞(MSCs)是基于细胞的移植和再生医学疗法的一个有前景的候选者。因此,在本研究中,华通氏胶间充质干细胞(WJ-MSCs)是在去除脐动脉和脐静脉后从胚胎外脐带基质中分离得到的。此外,为了克服因胎牛血清(FBS)的异种来源而补充FBS所带来的临床局限性,常规的FBS细胞培养补充剂已被人血小板裂解物(HPL)所取代。除了具有骨髓来源的MSCs的一般特征外,华通氏胶来源的MSCs在长期体外培养中具有维持表型特征、细胞生长动力学、细胞周期模式、体外多谱系分化可塑性、凋亡模式、正常核型等类似内在间充质干细胞特性的能力。此外,WJ-MSCs通过产生不仅是中胚层谱系的分化细胞,而且还有外胚层和内胚层谱系的细胞,展现出体外多谱系分化能力。而且,WJ-MSCs在SCID小鼠体内移植和体外软琼脂试验中未呈现任何异常细胞状态。与成人骨髓来源的MSCs相比,胎儿WJ-MSCs在暴露于炎性细胞因子时通过免疫调节因子的基因表达水平评估的免疫调节潜力相对较高。将接种在脱细胞羊膜支架上的WJ-MSCs移植到SCID小鼠模型的皮肤损伤处,结果表明,与单独的WJ-MSCs相比,WJ-MSCs与脱细胞羊膜支架的组合表现出显著更好的伤口愈合能力,瘢痕形成减少且有毛发生长,再生皮肤的生物力学性能得到改善。此外,我们的实验数据表明,最佳浓度的吲哚菁绿(ICG)可有效地用于干细胞标记以及通过标记移植细胞的近红外荧光非侵入性活细胞成像进行体内追踪,从而证明其在治疗应用中的效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b92/3988008/82cef4515f58/pone.0093726.g001.jpg

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