Molecular effect of human umbilical cord blood CD34-positive and CD34-negative stem cells and their conjugate in azoospermic mice

Abstract

Currently, azoospermia is one of the most common diseases of male infertility. Stem cell research is the new hope for novel therapy with a higher degree of safety and lower cost. This study aimed to investigate the effect of umbilical cord blood-derived stem cells (" and mesenchymal "UCB-MSCs") and mono-cell layer implanted into the induced azoospermic mice testis. Stem cells were isolated from umbilical cord blood and CD34+ve cells were separated from negative one by Mini MACs column. At 5th week after single injection of busulfan, stained mesenchymal (CD34-ve), hematopoietic stem cells (CD34+ve) and their conjugate (mono-cell layer) were injected locally into testis. At the end of the study, MSCs group showed that mRNA levels of genes related to meiosis (Vasa, SCP3, and PgK2) were increased with significant decrease of FSH and LH levels, compared to control group. Histologically, most of the tubules restored normal architecture. In contrast, HSCs and mono-cell layer groups showed statically insignificant change of FSH, LH, and gene expression, compared to control group. Histologically, distorted seminiferous tubules, with reduction in sperm content, and interstitial mononuclear cellular infiltration were seen. There was significant increase in the optical density of PCNA immune reaction in MSCs group than azoospermia, HSCs, and mono-cell layer, while there was non-significant difference between MSCs and control group. The present study suggested that injection of MSCs into chemotherapeutic-induced azoospermia in mice improved testicular failure; histologically and functionally, by restoration of spermatogenic gene expression while HSC and mono-cell layer showed no effect on spermatogenesis added to that mono-cell layer may induce testicular tissue damage.

Making gametes from alternate sources of stem cells: past, present and future

“…Following transplantation, partial reconstruction of seminiferous tubule architecture was observed. Abd Allah et al [ 68 ] The study evaluated the effect of transplantation of human cord blood derived mesenchymal cells (CD34-) and hematopoietic stem cells (CD34+) by local injection into testis of busulphan treated recipient mice. Testicular histoarchitecture was found normal and sperm were present in lumen in mesenchymal cells transplanted group compared to the HSC transplanted group.…”

Mesenchymal Stem Cell Therapy of Male Infertility

“…The last group of studies induces spermatogenesis using xenotransplantation of human umbilical cord MSCs in immunodeficient mice seminiferous tubule [41] or a combination of in vitro differentiation of induced pluripotent stem cells from mice and humans into germ cells, and also their transplantation was performed to obtain advanced differentiated spermatozoa [42]. Interestingly, the capability of human umbilical cord MSCs (UC-MSCs) for differentiation into germ cells in the lumen of seminiferous tubules of immunocompetent mice has been shown [41,43]. Furthermore, the therapeutic effects of BM-MSCs against toxic effects of lead (Pb) in the male gonads of rats have been shown [44].…”

Can mesenchymal stem cells ameliorate testicular damage? Current researches

“…Umbilical cord blood-derived hematopoietic stem cells (HSC, CD34 + cells) and UCMSCs (CD 34-cells) were transplanted into mice with busulfan-induced azoospermia, and increased expression of meiosis-associated genes were determined in the MSC transplanted group (Vasa, SCP3 and PgK2). The MSC group (CD34-) restored testicular injury by increasing spermatogenic gene expression, whereas the CD34 + group showed no activity [41]. Cadmium is a heavy metal used in industrial and agricultural production and may cause infertility by reducing the number of sperm on people exposed to this toxic substance.…”