Type I and II Diabetic Adipose-Derived Stem Cells Respond In Vitro to Dehydrated Human Amnion/Chorion Membrane Allograft Treatment by Increasing Proliferation, Migration, and Altering Cytokine Secretion

Abstract

Objective: Human amniotic membranes have been shown to be effective for healing diabetic foot ulcers clinically and to regulate stem cell activity in vitro and in vivo; however, diabetic stem cells may be impaired as a sequela of the disease. In this study, dehydrated human amnion/chorion membrane (dHACM) allografts (EpiFix®; MiMedx Group) were evaluated for their ability to regulate diabetic stem cells in vitro.Approach: Human adipose-derived stem cells (ADSCs) from normal, type I diabetic, and type II diabetic donors were treated with soluble extracts of dHACM and evaluated for proliferation after 3 days by DNA assay, chemotactic migration after 1 day by transwell assay, cytokine secretion after 3 days by multiplex ELISA, and gene expression after 5 days by reverse transcription–polymerase chain reaction.Results: Although diabetic ADSCs demonstrated decreased responses compared to normal ADSCs, dHACM treatment stimulated diabetic ADSCs to proliferate after 3 days and enhanced migration over 24 h, similar to normal ADSCs. dHACM-treated diabetic ADSCs modulated secretion of soluble signals, including regulators of inflammation, angiogenesis, and healing. All ADSCs evaluated also responded to dHACM treatment with altered expression of immunomodulatory genes, including interleukins (IL)-1α, IL-1β, and IL-1RA.Innovation: This is the first reported case demonstrating that diabetic ADSCs respond to novel amniotic membrane therapies, specifically treatment with dHACM.Conclusion: dHACM stimulated diabetic ADSCs to migrate, proliferate, and alter cytokine expression suggesting that, despite their diabetic origin, ADSCs may respond to dHACM to accelerate diabetic wound healing.

Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog?

“…Human adipose‐derived mesenchymal stem cells (hADMSCs) seeded onto radiosterilized human amnion have been tested in their ability to aid cutaneous wound repair in the form a biological bandage. In a study by Sánchez‐Sánchez and colleagues, AM were used as a biological scaffold for the culture and maintenance of hADMSCs, where the membranes were found to induce hADMSC to secrete IL‐10 as well as IL‐1β, whose interplay is thought to be vital for a balanced restoration of all necessary tissues . Decellularized AM has also been found to be suitable as a scaffold for the delivery of hADMSC in tissue engineering and regenerative medicine applications .…”

“…It is interesting to note that fetal membranes have also been used to support the growth of other stem cell types. Dehydrated fetal membranes consisting of both the amnion and chorion have been shown to support the proliferation and wound healing potential of adipose-derived stem cells from diabetic patients [98]. When implanted under the skin in a cutaneous ischemia model, the fetal membranes recruited circulating hematopoietic progenitor cells to sites of neovascularization [99].…”

Bioactivity and composition of a preserved connective tissue matrix derived from human placental tissue

“…This level of stimulation was consistent across four different samples and is similar to results from previous studies looking at placental membrane extracts. While previous research has shown the ability of extracts of other placenta tissue membrane products to stimulate migration of human umbilical vein endothelial cells, 61 ASCs, 62 and progenitor cells, 63 this is the first demonstration of this ability in a flowable placental tissue product.…”

Evaluation of dehydrated human umbilical cord biological properties for wound care and soft tissue healing

“…Fetal chorioamniotic membranes are widely accepted as a therapeutic option for the healing of cutaneous wounds due to their immunologically privileged status and bioactive properties . Although these fetal membranes have been successfully used for the treatment of chronic wounds, the umbilical cord has garnered increasing attention as an allograft for soft tissue healing .…”

“…This was performed by characterizing the composition of the tissue, evaluating in vitro cellular responses, including, stem cell proliferation, fibroblast migration, and angiogenic potential of endothelial cells, and assessing in vivo biocompatibility and resorption in a rat subcutaneous implantation model. PURION® PLUS Processed umbilical cord tissue (dHUC, EpiCord, MiMedx Group, Inc.) is processed using a similar technology to PURION® Processed dehydrated human amnion chorion membrane (dHACM; EpiFix/AmnioFix, MiMedx Group, Inc.) . Previous studies have demonstrated that this proprietary process results in an amniotic allograft with retained biological activity, which promotes accelerated wound closure of diabetic foot ulcers and venous leg ulcers when compared with standard treatments .…”