Effective Delivery of Stem Cells Using an Extracellular Matrix Patch Results in Increased Cell Survival and Proliferation and Reduced Scarring in Skin Wound Healing

Effective Delivery of Stem Cells Using an Extracellular Matrix Patch Results in Increased Cell Survival and Proliferation and Reduced Scarring in Skin Wound Healing
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DOI:
10.1089/ten.tea.2012.0480
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发表时间:
2013-03-01
影响因子:
4.1
通讯作者:
Longaker, Michael T.
Longaker, Michael T.
中科院分区:
医学3区
文献类型:
--
作者:
Lam, Mai T.;Nauta, Allison;Longaker, Michael T.

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伤口愈合是最复杂的生物过程之一,发生在身体的所有组织和器官中。在人类中,纤维化组织或瘢痕阻碍功能并且在美学上没有吸引力。干细胞疗法为帮助伤口愈合提供了一种有前途的新技术;然而,目前的研究结果表明,干细胞通常会死亡和/或从伤口部位迁移,大大降低了治疗效果。在这里,我们证明了干细胞疗法的有效性,通过使用天然贴片材料引入干细胞来改善皮肤中的伤口愈合并减少瘢痕形成。将脂肪来源的基质细胞引入到使用来自猪小肠粘膜下层(SIS)的非免疫原性细胞外基质(ECM)贴片材料在小鼠中创建的切除伤口中。SIS作为一种有吸引力的递送载体,因为其天然ECM成分,包括其胶原纤维网络,为干细胞提供了熟悉的结构。实验组由在创伤后不同时间点去除干细胞接种的贴片的伤口组成,以确定最佳治疗方案。通过体内生物发光成像证明,单独递送到皮肤伤口的干细胞在移植后不能存活。相比之下,用贴片递送能够显著增加干细胞增殖和存活。通过在贴片上用干细胞治疗,伤口愈合率得到适度改善;然而,与未治疗的伤口相比,在用贴片上的干细胞治疗的伤口中,纤维化区域(指示瘢痕形成)显著减少。
Wound healing is one of the most complex biological processes and occurs in all tissues and organs of the body. In humans, fibrotic tissue, or scar, hinders function and is aesthetically unappealing. Stem cell therapy offers a promising new technique for aiding in wound healing; however, current findings show that stem cells typically die and/or migrate from the wound site, greatly decreasing efficacy of the treatment. Here, we demonstrate effectiveness of a stem cell therapy for improving wound healing in the skin and reducing scarring by introducing stem cells using a natural patch material. Adipose-derived stromal cells were introduced to excisional wounds created in mice using a nonimmunogenic extracellular matrix (ECM) patch material derived from porcine small-intestine submucosa (SIS). The SIS served as an attractive delivery vehicle because of its natural ECM components, including its collagen fiber network, providing the stem cells with a familiar structure. Experimental groups consisted of wounds with stem cell-seeded patches removed at different time points after wounding to determine an optimal treatment protocol. Stem cells delivered alone to skin wounds did not survive post-transplantation as evidenced by bioluminescence in vivo imaging. In contrast, delivery with the patch enabled a significant increase in stem cell proliferation and survival. Wound healing rates were moderately improved by treatment with stem cells on the patch; however, areas of fibrosis, indicating scarring, were significantly reduced in wounds treated with the stem cells on the patch compared to untreated wounds.