Recent advances in the induced pluripotent stem cell‐based skin regeneration

Abstract

Skin regeneration has been a challenging clinical problem especially in cases of chronic wounds such as diabetic foot ulcers, and epidermolysis bullosa-related skin blisters. Prolonged non-healing wounds often lead to bacterial infections increasing the severity of wounds. Current treatment strategies for chronic wounds include debridement of wounds along with antibiotics, growth factors, and stem cell transplantation therapies. However, the compromised nature of autologous stem cells in patients with comorbidities such as diabetes limits the efficacy of the therapy. The discovery of induced pluripotent stem cell (iPSC) technology has immensely influenced the field of regenerative therapy. Enormous efforts have been made to develop integration-free iPSCs suitable for clinical therapies. This review focuses on recent advances in the methods and reprogramming factors for generating iPSCs along with the existing challenges such as genetic alterations, tumorigenicity, immune rejection, and regulatory hurdles for the clinical application of iPSCs. Furthermore, this review also highlights the benefits of using iPSCs for the generation of skin cells and skin disease modeling over the existing clinical therapies for skin regeneration in chronic wounds and skin diseases.

Reprogramming stem cells in regenerative medicine

“…(3) Tumorigenicity: one of the most critical clinical barriers to iPSC is that the genes responsible for the maintenance and pluripotency induction are also associated with cancer progression and therefore have the risk of inducing tumor formation after transplantation. 80 The oncogenic transformation of iPSC may also be due to the insertion of reprogramming vectors to overexpress pluripotency factors.…”

“…Furthermore, the expression levels of genes and proteins in PSC fluctuate continuously at a frequency of hours to days, and this heterogeneity reduces the reproducibility of studies. Therefore, there is a need to detect, mitigate, and control heterogeneity in experiments involving human PSC in future studies. Tumorigenicity: one of the most critical clinical barriers to iPSC is that the genes responsible for the maintenance and pluripotency induction are also associated with cancer progression and therefore have the risk of inducing tumor formation after transplantation 80 . The oncogenic transformation of iPSC may also be due to the insertion of reprogramming vectors to overexpress pluripotency factors.…”

The Emerging Role of Immune Cells and Targeted Therapeutic Strategies in Diabetic Wounds Healing

“…For wound healing, the most common treatment strategy involves transplantation of cells and growth factors into the wound area. 148 When transplanted into a wound, stem cells act in a direct and paracrine manner to promote cell recruitment, immunomodulation, extracellular matrix remodeling, and angiogenesis by secreting cytokines and growth factors. 149 , 150 However, due to the harsh microenvironment in DW, treatment strategies often fail.…”

Stem Cell-Based Tissue Engineering for the Treatment of Burn Wounds: A Systematic Review of Preclinical Studies

“…The vast majority of studies using a stem cell-based approach for treating burn wounds are at the preclinical testing stage, and vary widely in their methods and outcomes. Over the past three years, only a few reviews have discussed tissue engineering methods for skin repair, with a primary focus on biomaterials [ 33 ], murine models [ 34 ], pluripotent stem cells [ 32 ], or immunomodulation [ 31 ] and other signalling pathways [ 30 ]. This review will cover the latest advances in tissue engineered solutions involving adult stem cells, tested in a variety of preclinical models.…”

“…Embryonic stem cells (ESCs) and foetal stem cells (FSCs) are associated with moral concerns and substantial legal restrictions, slowing down their applications in clinical wound healing [ 30 , 31 ]. These and induced pluripotent stem cells (iPSCs) are also prone to teratoma formation due to their pluripotency depending on the efficiency of the differentiation protocol, raising potential safety concerns [ 32 ]. Hence, ESCs, FSCs and iPSCs have not been included in our analysis due to their current limitations in being used for clinical applications.…”