Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA.
J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
Microcirculation. 2021 Apr;28(3):e12672. doi: 10.1111/micc.12672. Epub 2020 Nov 29.
Restoration of form and function requires apposition of tissues in the form of flaps to reconstitute local perfusion. Successful reconstruction relies on flap survival and its integration with the recipient bed. The flap's precariously perfused hypoxic areas undergo adaptive microvascular changes both internally and in connection with the recipient bed. A cell-mediated, coordinated response to hypoxia drives these adaptive processes, restoring a tissue's normoxic homeostasis via de novo vasculogenesis, sprouting angiogenesis, and stabilizing arterialization. As cells exert prolonged and coordinated effects on site, their use as biological agents merit translational consideration of sourcing angio-competent cells and delivering them to territories enduring microcirculatory acclimatization. Angio-competent cells abound in adipose tissue: a reliable, accessible, and expendable source of adipose-derived cells (ADC). When subject to enzymatic digestion and centrifugation, adipose tissue separates its various ADC: A subset of buoyant oil-dense adipocytes (the tissue's parenchymal component) accumulates on a supra-natant layer, whereas the mesenchymal component remains in the infra-natant sediment, containing the tissue's stromal vascular fraction (SVF), where angio-component cells abound. The SVF can be further manipulated, selected, or culture expanded into more specific stromal subsets (herein defined as adipose stromal cells, ASC). While promising clinical applications for ADC await clinical proof and regulatory authorization, basic science investigation is needed to elucidate the specific ADC mechanisms that influence microvascular growth, remodeling, and function following flap surgery. The objective of this article is to share the clinical perspectives of reconstructive plastic surgeons regarding the use of ADC-based therapies to help with flap tissue integration, revascularization, and wound healing. Specifically, the focus will be on considering the potential for ADC as therapeutic agents and how their clinical application motivates basic science opportunities.
组织瓣的形式和功能的恢复需要通过皮瓣将组织对位来重新建立局部灌注。成功的重建依赖于皮瓣的存活及其与受区床的整合。皮瓣的灌注不稳定的缺氧区在内部和与受区床连接的地方经历适应性微血管变化。细胞介导的、协调的缺氧反应驱动这些适应性过程，通过新血管生成、发芽血管生成和稳定动脉化，恢复组织的正常氧合稳态。由于细胞在局部长时间协调地发挥作用，它们作为生物制剂的应用值得考虑从源头获取血管生成能力细胞并将其输送到需要微血管适应的区域。血管生成能力细胞在脂肪组织中大量存在：这是一种可靠、可及、可利用的脂肪来源细胞（ADCs）来源。经过酶消化和离心后，脂肪组织将其各种 ADC 分离出来：一部分浮力油密的脂肪细胞（组织的实质成分）聚集在上清层，而间质成分则留在下层沉淀物中，其中含有组织的基质血管部分（SVF），富含血管生成细胞。SVF 可以进一步进行操作、选择或培养扩增成更特异的基质亚群（此处定义为脂肪基质细胞，ASC）。虽然 ADC 的临床应用前景有待临床证实和监管部门授权，但仍需要基础科学研究来阐明影响皮瓣手术后微血管生长、重塑和功能的特定 ADC 机制。本文的目的是分享重建整形外科医生对基于 ADC 的治疗方法的临床观点，以帮助皮瓣组织整合、再血管化和伤口愈合。具体来说，重点将放在考虑 ADC 作为治疗剂的潜力以及它们的临床应用如何激发基础科学机会。
