Transplantation of alginate-encapsulated seminiferous tubules and interstitial tissue into adult rats: Leydig stem cell differentiation in vivo?

Abstract

In vivo and in vitro studies were conducted to determine whether testosterone-producing Leydig cells are able to develop from cells associated with rat seminiferous tubules, interstitium, or both. Adult rat seminiferous tubules and interstitium were isolated, encapsulated separately in alginate, and implanted subcutaneously into castrated rats. With implanted tubules, serum testosterone increased through two months. Tubules removed from the implanted rats and incubated with LH produced testosterone, and cells on the tubule surfaces expressed steroidogenic enzymes. With implanted interstitial tissue, serum levels of testosterone remained undetectable. However, co-culture of interstitium plus tubules in vitro resulted in the formation of Leydig cells by both compartments. These results indicate that seminiferous tubules contain both cellular and paracrine factors necessary for the differentiation of Leydig cells, and that the interstitial compartment contains precursor cells capable of forming testosterone-producing Leydig cells but requires stimulation by paracrine factors from the seminiferous tubules to do so.

Leydig cell stem cells: Identification, proliferation and differentiation

“…SLCs have been shown to be capable of giving rise to testosterone-producing Leydig cells in vivo, in locations outside testis (Chen et al, 2016). This could have clinical implications.…”

“…For example, if niche factors from the tubules were required for SLC proliferation and/or differentiation, such factors would not be present in preparations of interstitial tissue cultured in the absence of the tubules. To examine this possibility, we carried out a co-culture experiment in which the tubules and interstitial tissues were cultured in separate chambers that allowed a free exchange of paracrine factors between the two tissues (Chen et al, 2016). The co-culture of the interstitium with seminiferous tubules resulted in the production of testosterone-producing Leydig cells in the interstitial tissue.…”

Transdifferentiation of adult rat stem Leydig cells into prostatic and uterine epithelium, but not epidermis

“…The rodent testis contains SLCs that can form new Leydig cells and restore serum testosterone concentrations when differentiated Leydig cells are removed (Chen et al , 2016; Li et al , 2016). Our current results show that adult rSLCs are also able to differentiate into other non-Leydig cell types in vivo , in this case, prostatic and uterine epithelium, when exposed to appropriate inductive cues from fetal/neonatal mouse mesenchyme from other tissues.…”

“…In contrast, a previous study has shown that nestin-positive SLCs from neonatal mice can be programmed in vitro to form tissues of endodermal, mesodermal and ectodermal origin (Jiang et al , 2014). This may be due to age, experimental conditions ( in vitro vs in vivo ) and/or species of the SLCs used, since Jiang et al used neonatal mouse SLCs, in contrast to our adult rat SLCs (Stanley et al , 2012; Chen et al , 2016; Li et al , 2016). Previous studies have shown that the ability of differentiated epithelium to transdifferentiate decreases with age (Cunha, 1975; 1976).…”

Current Perspective and Advancements of Alginate-Based Transplantation Technologies

“…Other disease models have also used alginate microencapsulation for therapeutic use of xenogeneic stem cell-delivery. Researchers have reported functional alginate encapsulated adrenal SCs for use in adrenal hormone insufficiency diseases [63,64]. Successful alginate encapsulation of neural embryonic stem cells was also reported for targeted cell-delivery serving possible treatment for neural tissue repair in several neurological disorders [65].…”