Generation of human-induced pluripotent stem cells from burn patient-derived skin fibroblasts using a non-integrative method

Abstract

Patient specific induced pluripotent stem cells (iPSCs) have been recognized as a possible source of cells for skin tissue engineering. They have the potential to greatly benefit patients with large areas of burned skin or skin defects. However, the integration virus-based reprogramming method is associated with a high risk of genetic mutation and mouse embryonic fibroblast feeder-cells may be a pollutant. In the present study, human skin fibroblasts (HSFs) were successfully harvested from patients with burns and patient-specific iPSCs were generated using a non-integration method with a feeder-free approach. The octamer-binding transcription factor 4 (OCT4), sex-determining region Y box 2 (SOX2) and NANOG transcription factors were delivered using Sendai virus vectors. iPSCs exhibited representative human embryonic stem cell-like morphology and proliferation characteristics. They also expressed pluripotent markers, including OCT4, NANOG, SOX2, TRA181, stage-specific embryonic antigen 4 and TRA-160, and exhibited a normal karyotype. Teratoma and embryoid body formation revealed that iPSCs were able to differentiate into cells of all three germ layers in vitro and in vivo. The results of the present study demonstrate that HSFs derived from patients with burns, may be reprogrammed into stem cells with pluripotency, which provides a basis for cell-based skin tissue engineering in the future.

Generation of Functional Cardiomyocytes from Human Gastric Fibroblast-Derived Induced Pluripotent Stem Cells

“…The BJ cell derived from human neonatal foreskin has a high proliferation rate that minimized the shortage of low efficacy of reprogramming. Then, skin fibroblasts were widely used to generate iPSCs [ 25 , 26 ]. Here, we established a simple and universally applicable method to generate iPSCs from hGFCs.…”

Human-Induced Pluripotent Stem Cells in Plastic and Reconstructive Surgery

“…iPSC development provides new hope for patients with burns or large skin defects, as their treatment is are often limited by donor site availability and the quality of wound healing [38,39]. Fu et al harvested human skin fibroblasts from burn patients and successfully generated patient-specific iPSCs, providing an experimental basis for this potential future clinical application [40]. Another potential future application of iPSCs in plastic surgery is skin rejuvenation.…”

Haematopoietic stem cell reprogramming and the hope for a universal blood product

“…By 2008, several groups had adopted the technique, generating iPSCs that were considered epigenetically [44] and developmentally [45] indistinguishable from ESCs of murine [46], nonhuman primate (NHP) [47] and human origin [48,49]. To this day, pluripotent stem cell approaches to regenerative medicine have been proposed to address afflictions from cystic fibrosis [51][52][53] to diabetes [54][55][56] to third-degree burns [57][58][59]. To this day, pluripotent stem cell approaches to regenerative medicine have been proposed to address afflictions from cystic fibrosis [51][52][53] to diabetes [54][55][56] to third-degree burns [57][58][59].…”

“…Concern that cMyc would predispose iPSC-derived cells to malignant transformation was partially quashed when the TF was found to be dispensable to attain pluripotency [50]. To this day, pluripotent stem cell approaches to regenerative medicine have been proposed to address afflictions from cystic fibrosis [51][52][53] to diabetes [54][55][56] to third-degree burns [57][58][59].…”