This technology reprograms somatic cells, such as fibroblasts, into induced pluripotent stem cells (iPSCs) using non-integrative modified mRNA encoding key factors including OCT4, SOX2, KLF4, c-MYC, and VASA. The process involves daily transfections over 10–20 days, often supported by B18R protein to limit immune responses, thereby enhancing mRNA translation and reducing immunogenicity. Following reprogramming, the iPSCs are directly transplanted into the seminiferous tubules, where the Sertoli cell niche naturally drives their differentiation into male germ cells, including spermatogonia. Genetic modifications, such as correcting AZF deletions, can also be performed either before or after the transplantation step.
Description
This approach distinguishes itself by combining a non-integrative reprogramming technique with direct in vivo differentiation, which minimizes the risk of undifferentiated cell masses and teratoma formation typically seen in extended in vitro cultures. The inclusion of VASA in the reprogramming cocktail specifically augments the production of germ cells, offering both a promising therapeutic strategy for treating male infertility and a robust model for studying human germ cell development in a physiologically relevant environment.
Applications
Male infertility treatment
Regenerative reproductive medicine
Personalized fertility restoration
Genetic infertility correction
In vivo germ cell therapy
Advantages
Provides a potential therapeutic treatment for male infertility, including cases of non-obstructive azoospermia.
Uses a safe, non-integrative reprogramming method that minimizes genomic alterations.
Enables optional genetic modification to correct defects such as AZF deletions.
Promotes in vivo differentiation within the natural Sertoli cell niche, reducing the risk of teratoma formation.
Serves as a powerful research tool for advancing our understanding of human germ cell development.
IP Status
Abandoned -
https://patents.google.com/patent/US20160137975A1
