Transcriptomic and in vivo approaches introduced human iPSC-derived microvesicles for skin rejuvenation

Behnaz Bakhshandeh; Zohreh Jahanafrooz; Shiva Allahdadi; Shiva Daryani; Zahra Dehghani; Mahya Sadeghi; Mir Sepehr Pedram; Mohammad Mehdi Dehghan

doi:10.1038/s41598-023-36162-9

Transcriptomic and in vivo approaches introduced human iPSC-derived microvesicles for skin rejuvenation

Sci Rep. 2023 Jun 20;13(1):9963. doi: 10.1038/s41598-023-36162-9.

Authors

Behnaz Bakhshandeh¹, Zohreh Jahanafrooz², Shiva Allahdadi³, Shiva Daryani³, Zahra Dehghani⁴, Mahya Sadeghi⁵, Mir Sepehr Pedram^{6

7}, Mohammad Mehdi Dehghan^{6

7}

Affiliations

¹ Department of Biotechnology, College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran. b.bakhshandeh@ut.ac.ir.
² Department of Biology, Faculty of Sciences, University of Maragheh, Maragheh, Iran.
³ Department of Cellular and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
⁴ Department of Biotechnology, College of Science, University of Tehran, P.O. Box 14155-6455, Tehran, Iran.
⁵ Department of Biomedical Engineering, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
⁶ Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
⁷ Institute of Biomedical Research, University of Tehran, Tehran, Iran.

Abstract

The skin undergoes the formation of fine lines and wrinkles through the aging process; also, burns, trauma, and other similar circumstances give rise to various forms of skin ulcers. Induced pluripotent stem cells (iPSCs) have become promising candidates for skin healing and rejuvenation due to not stimulating inflammatory responses, low probability of immune rejection, high metabolic activity, good large-scale production capacity and potentials for personalized medicine. iPSCs can secrete microvesicles (MVs) containing RNA and proteins responsible for the normal repairing process of the skin. This study aimed to evaluate the possibility, safety and effectiveness of applying iPSCs-derived MVs for skin tissue engineering and rejuvenation applications. The possibility was assessed using the evaluation of the mRNA content of iPSC-derived MVs and the behavior of fibroblasts after MV treatment. Investigating the effect of microvesicle on stemness potential of mesenchymal stem cells was performed for safety concerns. In vivo evaluation of MVs was done in order to investigate related immune response, re-epithelialization and blood vessel formation to measure effectiveness. Shedding MVs were round in shape distributed in the range from 100 to 1000 nm in diameter and positive for AQP3, COL2A, FGF2, ITGB, and SEPTIN4 mRNAs. After treating dermal fibroblasts with iPSC-derived MVs, the expressions of collagens Iα1 and III transcripts (as the main fibrous extracellular matrix (ECM) proteins) were upregulated. Meanwhile, the survival and proliferation of MV treated fibroblasts did not change significantly. Evaluation of stemness markers in MV treated MSCs showed negligible alteration. In line with in vitro results, histomorphometry and histopathology findings also confirmed the helpful effect of MVs in skin regeneration in the rat burn wound models. Conducting more investigations on hiPSCs-derived MVs may lead to produce more efficient and safer biopharmaceutics for skin regeneration in the pharmaceutical market.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell-Derived Microparticles* / metabolism
Humans
Induced Pluripotent Stem Cells* / metabolism
Rats
Rejuvenation
Skin / pathology
Transcriptome