Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Plastic Surgery, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
J Tissue Eng Regen Med. 2019 Jun;13(6):973-985. doi: 10.1002/term.2843. Epub 2019 Apr 15.
Fat grafting is an established clinical intervention to promote tissue repair. The role of the fat's extracellular matrix (ECM) in regeneration is largely neglected. We investigated in vitro the use of human adipose tissue-derived ECM hydrogels as release platform for factors secreted by adipose-derived stromal cells (ASCs). Lipoaspirates from nondiabetic and diabetic donors were decellularized. Finely powdered acellular ECM was evaluated for cell remainders and DNA content. Acellular ECM was digested, and hydrogels were formed at 37°C and their viscoelastic relaxation properties investigated. Release of ASC-released factors from hydrogels was immune assessed, and bio-activity was determined by fibroblast proliferation and migration and endothelial angiogenesis. Acellular ECM contained no detectable cell remainders and negligible DNA contents. Viscoelastic relaxation measurements yielded no data for diabetic-derived hydrogels due to gel instability. Hydrogels released several ASC-released factors concurrently in a sustained fashion. Functionally, released factors stimulated fibroblast proliferation and migration as well as angiogenesis. No difference between nondiabetic and diabetic hydrogels in release of factors was measured. Adipose ECM hydrogels incubated with released factors by ASC are a promising new therapeutic modality to promote several important wound healing-related processes by releasing factors in a controlled way.
脂肪移植是一种成熟的临床干预手段，可促进组织修复。脂肪细胞外基质 (ECM) 在再生中的作用在很大程度上被忽视了。我们在体外研究了人脂肪组织衍生的 ECM 水凝胶作为脂肪来源基质细胞 (ASC) 分泌因子的释放平台的用途。来自非糖尿病和糖尿病供体的脂肪抽吸物进行去细胞化处理。对无细胞 ECM 的细粉进行细胞残留物和 DNA 含量评估。对无细胞 ECM 进行消化，在 37°C 下形成水凝胶，并研究其粘弹性松弛特性。通过免疫评估水凝胶中 ASC 释放因子的释放情况，并通过成纤维细胞增殖和迁移以及内皮血管生成来确定其生物活性。无细胞 ECM 中未检测到可检测的细胞残留物和可忽略不计的 DNA 含量。由于凝胶不稳定，无法获得糖尿病衍生水凝胶的粘弹性松弛测量数据。水凝胶以持续的方式同时释放多种 ASC 释放因子。功能上，释放的因子刺激成纤维细胞增殖、迁移和血管生成。在释放因子方面，未在糖尿病和非糖尿病水凝胶之间测量到差异。与 ASC 释放因子孵育的脂肪 ECM 水凝胶是一种很有前途的新治疗方式，通过以可控的方式释放因子来促进几种重要的与伤口愈合相关的过程。
