Transplantation of encapsulated human Leydig-like cells: A novel option for the treatment of testosterone deficiency

Mol Cell Endocrinol. 2021 Jan 1:519:111039. doi: 10.1016/j.mce.2020.111039. Epub 2020 Sep 24.

Abstract

Previous studies have demonstrated that the transplantation of alginate-poly-ʟ-lysine-alginate (APA)-encapsulated rat Leydig cells (LCs) provides a promising approach for treating testosterone deficiency (TD). Nevertheless, LCs have a limited capacity to proliferate, limiting the efficacy of LC transplantation therapy. Here, we established an efficient differentiation system to obtain functional Leydig-like cells (LLCs) from human stem Leydig cells (hSLCs). Then we injected APA-encapsulated LLCs into the abdominal cavities of castrated mice without an immunosuppressor. The APA-encapsulated cells survived and partially restored testosterone production for 90 days in vivo. More importantly, the transplantation of encapsulated LLCs ameliorated the symptoms of TD, such as fat accumulation, muscle atrophy and adipocyte accumulation in bone marrow. Overall, these results suggest that the transplantation of encapsulated LLCs is a promising new method for testosterone supplementation with potential clinical applications in TD.

Keywords: Alginate-poly-ʟ-lysine-alginate; Encapsulation; Human stem Leydig cells; Hypogonadism; Leydig-like cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / pathology
  • Adolescent
  • Adult
  • Aged
  • Alginates / chemistry
  • Antigens, CD / metabolism
  • Bone Marrow / pathology
  • Capsules
  • Castration
  • Cell Differentiation
  • Cells, Immobilized / transplantation*
  • Humans
  • Leydig Cells / transplantation*
  • Leydig Cells / ultrastructure
  • Male
  • Middle Aged
  • Muscular Atrophy / pathology
  • Polylysine / analogs & derivatives
  • Polylysine / chemistry
  • Testosterone / deficiency*
  • Testosterone / metabolism
  • Young Adult

Substances

  • Alginates
  • Antigens, CD
  • Capsules
  • alginate-polylysine-alginate
  • Polylysine
  • Testosterone