Review of injection techniques for spermatogonial stem cell transplantation

Abstract

BACKGROUND Although the prognosis of childhood cancer survivors has increased dramatically during recent years, chemotherapy and radiation treatments for cancer and other conditions may lead to permanent infertility in prepubertal boys. Recent developments have shown that spermatogonial stem cell (SSC) transplantation may be a hope for restoring fertility in adult survivors of childhood cancers. For this reason, several centres around the world are collecting and cryopreserving testicular tissue or cells anticipating that, in the near future, some patients will return for SSC transplantation. This review summarizes the current knowledge and utility of SSC transplantation techniques. OBJECTIVE AND RATIONALE The aim of this narrative review is to provide an overview of the currently used experimental injection techniques for SSC transplantation in animal and human testes. This is crucial in understanding and determining the role of the different techniques necessary for successful transplantation. SEARCH METHODS A comprehensive review of peer-reviewed publications on this topic was performed using the PubMed and Google Scholar databases. The search was limited to English language work and studies between 1994 (from the first study on SSC transplantation) and April 2019. Key search terms included mouse, rat, boar, ram, dog, sheep, goat, cattle, monkey, human, cadaver, testes, SSC transplantation, injection and technique. OUTCOMES This review provides an extensive clinical overview of the current research in the field of human SSC transplantation. Rete testis injection with ultrasonography guidance currently seems the most promising injection technique thus far; however, the ability to draw clear conclusions is limited due to long ischemia time of cadaver testis, the relatively decreased volume of the testis, the diminishing size of seminiferous tubules, a lack of intratesticular pressure and leakage into the interstitium during the injection on human cadaver testis. Current evidence does not support improved outcomes from multiple infusions through the rete testes. Overall, further optimization is required to increase the efficiency and safety of the infusion method. WIDER IMPLICATIONS Identifying a favourable injection method for SSC transplantation will provide insight into the mechanisms of successful assisted human reproduction. Future research could focus on reducing leakage and establishing the optimal infusion cell concentrations and pressure.

Cellular Therapy via Spermatogonial Stem Cells for Treating Impaired Spermatogenesis, Non-Obstructive Azoospermia

“…Brinster and colleagues were the first to identify a technique for transplanting SSCs [ 120 ]. Fertility preservation in rodents after SSC transplantation indicates that this technique could have medical application in humans [ 83 , 121 ]. The critical points are the success of SSCs storage (good cryopreservation) and transplantation, and when transplanted, induction of spermatogenesis [ 122 ].…”

Spermatogonial Stem Cell Transplantation in Large Animals

“…SSCs can either be injected into the efferent ducts connecting the rete tubules and epididymis, the rete tubules formed by the convergent ends of all seminiferous tubes, or the seminiferous tubes themselves [10,92]. In most mammals, testicular lobules are closed compartments formed by the tunica albuginea extending inward and separating the testes, where the seminiferous tubules exist in a highly coiled and tightly packed manner [92][93][94]. A precise injection of donor cells into the lumen of seminiferous tubules may require multiple incisions in the tunica albuginea, which increases the complexity of the manipulation and injury to the testis of recipient [10].…”

“…A precise injection of donor cells into the lumen of seminiferous tubules may require multiple incisions in the tunica albuginea, which increases the complexity of the manipulation and injury to the testis of recipient [10]. Also, the potential increase of the intratubular pressure during the injection process may cause rupture of the membrane [92]. With regard to efferent tubules, the efferent tubules in rodents usually merge and form a single common efferent tubule connected to the epididymal head, providing easy access for injection into the common route.…”

“…With regard to efferent tubules, the efferent tubules in rodents usually merge and form a single common efferent tubule connected to the epididymal head, providing easy access for injection into the common route. However, in large animals, multiple efferent tubules enter the epididymal head in parallel, which may complicate injection through the efferent tubule [92]. The rete testis has a distinct structure in testis, making it easily distinguishable from the surrounding tissues and offering more practical access to the seminiferous tubules [12].…”

“…However, the anatomical structure of rete testis differs among species. In rodents, including mice, rats, and hamsters, the rete testis is located closer to the subcapsular area, while in most other species, such as cats, dogs, rams, bulls, boars, and monkeys, the rete testis is located longitudinally and deeply in the center of the testis [10,92,95]. Therefore, the rete testis is more difficult to access and visualize in large animals compared with rodents, and imaging techniques such as ultrasound imaging are required for a precise injection.…”