Isolation and Characterization of Novel, Highly Proliferative Human CD34/CD73-Double-Positive Testis-Derived Stem Cells for Cell Therapy

Abstract

Human adult stem cells are a readily available multipotent cell source that can be used in regenerative medicine. Despite many advantages, including low tumorigenicity, their rapid senescence and limited plasticity have curtailed their use in cell-based therapies. In this study, we isolated CD34/CD73-double-positive (CD34(+)/CD73(+)) testicular stromal cells (HTSCs) and found that the expression of CD34 was closely related to the cells' stemness and proliferation. The CD34(+)/CD73(+) cells grew in vitro for an extended period of time, yielding a multitude of cells (5.6×10(16) cells) without forming tumors in vivo. They also differentiated into all three germ layer lineages both in vitro and in vivo, produced cartilage more efficiently compared to bone marrow stem cells and, importantly, restored erectile function in a cavernous nerve crush injury rat model. Thus, these HTSCs may represent a promising new autologous cell source for clinical use.

Current Perspectives on Stem Cell Therapy for Erectile Dysfunction

“…Choi et al evaluated this cellular subset, finding that CD34-and CD73-positive cells exhibited longer proliferative capacity and greater differentiation potential in cells of adipogenic, osteogenic, neuronal, and pancreatic lineages. 44 As a further beneficial result, these cells did not lead to the formation of teratomas in immunodeficient mice, as was seen in a previous study with stem cells isolated from the testes. 43 Choi et al also has been the only study to evaluate the use of TDSCs in improving erectile function.…”

“…The remaining interstitial cells are collected, filtered, and plated in gelatin-coated flasks and cultured in TDSC-specific medium. 42,44 TDSCs have been found to have varying cellular biomarkers; this, in part, explains the differing replicative potential in studies. Spermatogonial stem cells, for example, are positive for GPR-125 and GFRa1.…”

“…43 Choi et al also has been the only study to evaluate the use of TDSCs in improving erectile function. 44 By injecting these CD34 þ /CD73 þ stem cells periprostatically into rats where the cavernous nerve had been crushed, they evaluated functional recovery based on nerve stimulation and intracavernous pressure. The researchers found that the mean ICP/MAP ratios were significantly lower in the injury group compared to the sham, and that the group injected with TDSCs exhibited partial recovery.…”

Advances in Stem Cell Therapy for Erectile Dysfunction

“…A recently published study demonstrated the isolation of SCs from human testis [111]. These cells were positive for CD34 and localized to the testicular stroma; therefore, they are most likely MSCs.…”

The Current Status of Stem-Cell Therapy in Erectile Dysfunction: A Review

“…Direct injection into the major pelvic ganglia has not been methodically studied due to the inherent challenges involved in the injection process [3761]. Periprostatic injection, with or without a concurrent intracorporal injection, has also been attempted [626364]. Intraperitoneal infusion of stem cells was less efficacious than intracorporal injection in improving erectile function in a CN injury mouse model, though both groups did show improvement from baseline values [6566].…”