The potential and limitations of induced pluripotent stem cells to achieve wound healing

Abstract

Wound healing is the physiologic response to a disruption in normal skin architecture and requires both spatial and temporal coordination of multiple cell types and cytokines. This complex process is prone to dysregulation secondary to local and systemic factors such as ischemia and diabetes that frequently lead to chronic wounds. Chronic wounds such as diabetic foot ulcers are epidemic with great cost to the healthcare system as they heal poorly and recur frequently, creating an urgent need for new and advanced therapies. Stem cell therapy is emerging as a potential treatment for chronic wounds, and adult-derived stem cells are currently employed in several commercially available products; however, stem cell therapy is limited by the need for invasive harvesting techniques, immunogenicity, and limited cell survival in vivo. Induced pluripotent stem cells (iPSC) are an exciting cell type with enhanced therapeutic and translational potential. iPSC are derived from adult cells by in vitro induction of pluripotency, obviating the ethical dilemmas surrounding the use of embryonic stem cells; they are harvested non-invasively and can be transplanted autologously, reducing immune rejection; and iPSC are the only cell type capable of being differentiated into all of the cell types in healthy skin. This review focuses on the use of iPSC in animal models of wound healing including limb ischemia, as well as their limitations and methods aimed at improving iPSC safety profile in an effort to hasten translation to human studies.

The Treatment of Impaired Wound Healing in Diabetes: Looking among Old Drugs

“…More recently, the use of induced pluripotent stem cells (iPSC) has emerged as a novel cellular therapy with the advantage of being potentially an autologous transplant with low rate of immune rejection. A large body of data is provided by several preclinical studies carried out in animal models of wound healing [47] that make promising the opportunity to translate iPSC into a new therapeutic tool for wound healing also in humans in the near future.…”

Induced Pluripotent Stem Cells in Dental and Nondental Tissue Regeneration: A Review of an Unexploited Potential

“…Initial reports documented that the risk of teratoma formation associated with iPSC transplantation could be inhibited by pretreatment with resveratrol [112] or by irradiation of 2 Gray (Gy) prior to transplantation [43]. Finally, iPSCs' extracellular vesicles and secretomes, containing protein, mRNA, and miRNA, can alternatively be used, exploiting the paracrine effect of iPSCs while avoiding the risk of tumorigenesis associated with iPSC-based therapy [160].…”

“…iPSCs' extracellular vesicles, containing protein, mRNA, and miRNA, can further be used in regenerative medicine, seizing the paracrine effect of iPSCs while avoiding the possible risk of tumorigenesis associated with iPSC-based therapy [160]. The paracrine role of iPSCs in salivary gland regeneration has been proven upon coculturing embryonic submandibular gland cells and mouse iPSCs [124].…”

An In situ Collagen-HA Hydrogel System Promotes Survival and Preserves the Proangiogenic Secretion of hiPSC-derived Vascular Smooth Muscle Cells

“…Vascular smooth muscle cells derived from integration-free human iPSCs are transforming the field of vascular tissue engineering and regenerative healing with enormous translational potential (B. C. Dash, Z. Jiang, C. Suh, & Y. Qyang, 2015a; Gorecka et al, 2019). Most recently, our studies revealed the proangiogenic and anti-inflammatory potential of these cells and their use in the treatment of acute and chronic wounds (Dash et al, 2020; Gorecka et al, 2020).…”