Autologous Adipose Stromal Cells Seeded onto a Human Collagen Matrix for Dermal Regeneration in Chronic Wounds: Clinical Proof of Concept
Autologous Adipose Stromal Cells Seeded onto a Human Collagen Matrix for Dermal Regeneration in Chronic Wounds: Clinical Proof of Concept
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DOI：
10.1097/prs.0000000000001437
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发表时间：
2015-08-01
影响因子：
3.6
通讯作者：
Dufrane, Denis
中科院分区：
文献类型：
--
作者：
Lafosse, Aurore;Desmet, Celine;Dufrane, Denis
背景：不愈合的伤口无法通过无血管和纤维化真皮组织整合皮肤自体移植物。脂肪源性基质细胞可以通过血管生成和免疫调节来改善创面床的局部环境。这项工作旨在开发一种由脂肪源性基质细胞在人无细胞胶原基质上制成的生物敷料。方法：从人脂肪组织中分离出脂肪源性基质细胞（n = 8）。在体外，评估了早期和晚期传代（1、4、10和16）期间的遗传稳定性以及血管内皮生长因子（VEGF）分泌。初步研究了脂肪基质细胞在胶原基质上的粘附和铺展。将构建体植入裸鼠（n = 10）后，评估体内致瘤性、血管生成和组织氧合。生物敷料被制造出来并植入三名慢性伤口患者体内。结果：在体外，直到细胞传代晚期都检测到非整倍体，但没有克隆转化。缺氧（0.1% 氧气）期间 VEGF 的分泌量高于常氧（21% 氧气）期间的 VEGF 分泌量。脂肪来源的基质细胞可以在 18 至 20 天内在支架上粘附和扩散。在免疫功能低下的大鼠中植入后3个月没有发生肿瘤。脂肪源性基质细胞植入后，血管计数和组织氧合作用更高。在患者体内发现了肉芽组织（血管密度的 276%），随后在植入后长达 22 个月内进行上皮化或分层皮肤移植。结论：将脂肪源性基质细胞接种到人脱细胞胶原基质（生物敷料）上进行植入，是治疗不愈合伤口的一种有前途的疗法，可改善真皮血管生成和重塑。这种使用自体基质细胞的疗法是安全的，体外扩增后不会发生显着的遗传改变。
Background: Nonhealing wounds are unable to integrate skin autografts by avascular and fibrotic dermal tissue. Adipose-derived stromal cells can improve the local environment of the wound bed by angiogenesis and immunomodulation. This work aimed to develop a biological dressing made of adipose-derived stromal cells onto a human acellular collagen matrix.Methods: Adipose-derived stromal cells were isolated from human adipose tissue (n = 8). In vitro, the genetic stability during early and late passages (1, 4, 10, and 16) and vascular endothelial growth factor (VEGF) secretion were assessed. Adipose-derived stromal cell adhesion and spreading on collagen matrix were preliminarily studied. In vivo tumorigenicity, angiogenesis, and tissue oxygenation were assessed after implantation of the construct in nude rats (n = 10). The biological dressing was manufactured and implanted in three patients with chronic wounds.Results: In vitro, aneuploidies, but no clonal transformation, were detected up to late cellular passages. VEGF was secreted more during hypoxia (0.1% oxygen) than during normoxia (21% oxygen). Adipose-derived stromal cells can adhere and spread on the scaffold within 18 to 20 days. No tumor development occurred 3 months after implantation in immunocompromised rats. Vessel counts and tissue oxygenation were higher after adipose-derived stromal cell implantation. In patients, granulation tissue was found (276 percent of vessel density), followed by epithelialization or split-thickness skin engraftment up to 22 months after implantation.Conclusions: Implantation of adipose-derived stromal cells seeded onto human acellular collagen matrix (biological dressing) represents a promising therapy for nonhealing wounds, offering improvement in dermal angiogenesis and remodeling. This therapy using autologous stromal cells is safe, without significant genetic alterations after in vitro expansion.