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人胎儿间充质干细胞群体的分离和鉴定:探索在创伤愈合治疗中细胞库存储的潜力。

Isolation and Characterization of a Human Fetal Mesenchymal Stem Cell Population: Exploring the Potential for Cell Banking in Wound Healing Therapies.

机构信息

Departments of Surgery and Bioengineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh, PA, USA.

The University of Pittsburgh Medical Center, UPMC Mercy Hospital Trauma and Burn Centers, Pittsburgh, PA, USA.

出版信息

Cell Transplant. 2019 Nov;28(11):1404-1419. doi: 10.1177/0963689718817524. Epub 2019 Aug 13.

Abstract

Various cell-based therapies are in development to address chronic and acute skin wound healing, for example for burns and trauma patients. An off-the-shelf source of allogeneic dermal cells could be beneficial for innovative therapies accelerating the healing in extensive wounds where the availability of a patient's own cells is limited. Human fetal-derived dermal fibroblasts (hFDFs) show high in vitro division rates, exhibit low immunological rejection properties, and present scarless wound healing in the fetus, and previous studies on human fetal tissue-derived cell therapies have shown promising results on tissue repair. However, little is known about cell lineage stability and cell differentiation during the cell expansion process, required for any potential therapeutic use. We describe an isolation method, characterize a population, and investigate its potential for cell banking and thus suitability as a potential product for cell grafting therapies. Our results show hFDFs and a bone marrow-derived mesenchymal stem cell (BM-MSC) line shared identification markers and in vitro multilineage differentiation potential into osteogenic, chondrogenic, and adipogenic lineages. The hFDF population exhibited similar cell characteristics as BM-MSCs while producing lower pro-inflammatory cytokine IL-6 levels and higher levels of the wound healing factor hepatocyte growth factor. We demonstrate in vitro differentiation of hFDFs, which may be a problem in maintaining long-term lineage stability, potentially limiting their use for cell banking and therapy development.

摘要

各种基于细胞的疗法正在开发中,以解决慢性和急性皮肤伤口愈合问题,例如烧伤和创伤患者。现成的同种异体真皮细胞来源可能有益于创新疗法,加速广泛伤口的愈合,而患者自身细胞的可用性有限。人胎儿来源的真皮成纤维细胞(hFDF)具有较高的体外分裂率,表现出较低的免疫排斥特性,并且在胎儿中实现无瘢痕的伤口愈合,以前对人胎儿组织来源的细胞疗法的研究表明在组织修复方面具有有前景的结果。然而,对于任何潜在的治疗用途,在细胞扩增过程中细胞谱系稳定性和细胞分化的了解甚少。我们描述了一种分离方法,对其进行了特征描述,并研究了其用于细胞储存的潜力,以及作为细胞移植治疗潜在产品的适用性。我们的结果表明,hFDF 和骨髓来源的间充质干细胞(BM-MSC)系具有共同的鉴定标记,并具有体外多谱系分化为成骨细胞、软骨细胞和脂肪细胞谱系的潜力。hFDF 群体表现出与 BM-MSCs 相似的细胞特征,同时产生较低的促炎细胞因子 IL-6 水平和较高的伤口愈合因子肝细胞生长因子水平。我们证明了 hFDF 的体外分化,这可能是维持长期谱系稳定性的问题,可能限制了它们用于细胞储存和治疗开发的用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/00c8/6802149/2520e34a62db/10.1177_0963689718817524-fig1.jpg

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