Generation of niche tuned antifibrotic fibroblasts and non‐viral mediated endothelial commitment using adipose stem cells for dermal graft development

Abstract

Cell‐based skin substitute generation has seen considerable development. Combining synthetic scaffolds with biomimetic fibrin does direct both exogenous and endogenous stem cell differentiation, addressing needs for reliable tissue engineering. However, lack of immediate vasculature within implantable grafts remains critical for its sustenance and integration. Multipotency, high proliferation potential, ability to release multiple growth factors (GFs), and autologous availability highlight the use of human adipose derived mesenchymal stem cells (hADMSCs) in tissue‐engineered dermal grafts (TEDG) construction. However, hADMSCs' insufficiency to independently establish angiogenesis within tissue constructs demands improvement of stem cell application for dermal graft survival. Approaches to harness microenvironmentally sensitive paracrine interactions could improve the angiogenic efficiency of hADMSCs within TEDG. This study conceptualized a fibrin‐based niche, to direct hADMSCs toward a nonfibrotic fibroblast commitment and incorporation of bioengineered hADMSCs, specifically releasing potent angiogenic factors within TEDG. Coexistence of tuned fibroblast and endothelial lineage committed cells contributed to well‐regulated extracellular matrix formation and prevascularization. Adequate cell proliferation; sustained transient release of angiogenic GFs till 20 days; directed dermal, endothelial, fibroblast, and vascular smooth muscle cell differentiation; and favored elastin and collagen deposition were achieved in vitro. In conclusion, specific niche composition and employment of bioengineered hADMSCs favor implantable TEDG construction.

Human-Derived Scaffold Components and Stem Cells Creating Immunocompatible Dermal Tissue Ensuing Regulated Nonfibrotic Cellular Phenotypes

“…The reference numbers of study approvals obtained from SCTIMST are SCT/IC-SCR/45/March2017 and IEC NO: SCT/IEC/1231/June 2018. All approvals from KIMS and SCTIMST are linked to the guidelines stipulated by Indian Council for Medical Research, Government of India. Validate the in vitro tissue engineering potential of AMFIBHA scaffold using fibroblasts (human adipose tissue-derived mesenchymal stem cells (hADMSCs)-derived fibroblasts). Briefly, isolate hADMSCs for developing fibroblast from lipoaspirates from healthy human subjects. Differentiate hADMSC fibroblast as per the published protocol using a fibroblast specific niche. , Use a cell density of 5000 cells/cm 2 for the in vitro evaluations. …”

Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

“…Accordingly, the development of a capillary-like network and lumen formation was observed within a week that eventually promoted repair of the rat cranial bone defects ( Xu et al, 2019 ). Moreover, MSC-derived CD31 + endothelial cells in culture with AD-MSCs and MSC-derived fibroblasts were successfully used for prevascularizing a fibroblast niche coated tissue engineered dermal graft (TEDG) scaffold, which was developed as a skin substitute ( Ajit et al, 2020 ). In another study, Masuda et al developed a cardiac cell sheet using rat embryonic stem cell-derived ECs, dermal fibroblasts and embryonic stem cell-derived cardiomyocytes.…”