Identification and characterization of stem cell secretome-based recombinant proteins for wound healing applications

Abstract

Stem cells have been introduced as a promising therapy for acute and chronic wounds, including burn injuries. The effects of stem cell-based wound therapies are believed to result from the secreted bioactive molecules produced by stem cells. Therefore, treatments using stem cell-derived conditioned medium (CM) (referred to as secretome) have been proposed as an alternative option for wound care. However, safety and regulatory concerns exist due to the uncharacterized biochemical content and variability across different batches of CM samples. This study presents an alternative treatment strategy to mitigate these concerns by using fully characterized recombinant proteins identified by the CM analysis to promote pro-regenerative healing. This study analyzed the secretome profile generated from human placental stem cell (hPSC) cultures and identified nine predominantly expressed proteins (ANG-1, FGF-7, Follistatin, HGF, IL-6, Insulin, TGFβ-1, uPAR, and VEGF) that are known to contribute to wound healing and angiogenesis. These proteins, referred to as s (CMFs), were used in combination to test the effects on human dermal fibroblasts (HDFs). Our results showed that CMF treatment increased the HDF growth and accelerated cell migration and wound closure, similar to stem cell and CM treatments. In addition, the CMF treatment promoted angiogenesis by enhancing new vessel formation. These findings suggest that the defined CMF identified by the CM proteomic analysis could be an effective therapeutic solution for wound healing applications. Our strategy eliminates the regulatory concerns present with stem cell-derived secretomes and could be developed as an off-the-shelf product for immediate wound care and accelerating healing.

3D Printed Eggshell Microparticle-Laden Thermoplastic Scaffolds for Bone Tissue Engineering

“…The normalized results were used to analyze the effect of ESP concentration on cell proliferation. Based on the previously published literature examples, we normalized our metabolic activity data to day 0. − An initial significant increase in metabolic activity was observed on day 3 for ESP-0, ESP-15, and ESP-50, while the increase in the value was significant within all groups on days 7 and 14. However, there was a decrease in the value for ESP-15 compared with the other groups on day 14.…”

The Potential of MSC-Based Cell-Free Therapy in Wound Healing—A Thorough Literature Review

“…Another study demonstrated that CM from bone marrow-derived stem cells reduced the inflammatory cells (neutrophils and macrophages) infiltration in vivo at various time points [60]. A group of proteins related to inflammation have been identified in MSCs-derived secretome (Table 1) [59][60][61][62][63][64].…”