Stem Cell Biology Department, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.
Indian J Med Res. 2018 Dec;148(Suppl):S38-S49. doi: 10.4103/ijmr.IJMR_2065_17.
A large proportion of patients who survive cancer are rendered infertile as an unwanted side effect of oncotherapy. Currently accepted approaches for fertility preservation involve banking eggs/sperm/embryos or ovarian/testicular tissue before oncotherapy for future use. Such approaches are invasive, expensive, technically challenging and depend on assisted reproductive technologies (ART). Establishing a gonadal tissue bank (for cancer patients) is also fraught with ethical, legal and safety issues. Most importantly, patients who find it difficult to meet expenses towards cancer treatment will find it difficult to meet expenses towards gonadal tissue banking and ART to achieve parenthood later on. In this review an alternative strategy to regenerate non-functional gonads in cancer survivors by targeting endogenous stem cells that survive oncotherapy is discussed. A novel population of pluripotent stem cells termed very small embryonic-like stem cells (VSELs), developmentally equivalent to late migratory primordial germ cells, exists in adult gonads and survives oncotherapy due to their quiescent nature. However, the stem-cell niche gets compromised by oncotherapy. Transplanting niche cells (Sertoli or mesenchymal cells) can regenerate the non-functional gonads. This approach is safe, has resulted in the birth of fertile offspring in mice and could restore gonadal function early in life to support proper growth and later serve as a source of gametes. This newly emerging understanding on stem cells biology can obviate the need to bank gonadal tissue and fertility may also be restored in existing cancer survivors who were earlier deprived of gonadal tissue banking before oncotherapy.
很大一部分癌症幸存者由于肿瘤治疗的副作用而不孕不育。目前，为了将来使用，保留生育力的方法包括在肿瘤治疗前储存卵子/精子/胚胎或卵巢/睾丸组织。这些方法具有侵袭性、昂贵、技术挑战性，并且依赖于辅助生殖技术（ART）。建立生殖腺组织库（用于癌症患者）也存在伦理、法律和安全问题。最重要的是，对于那些难以负担癌症治疗费用的患者来说，他们也难以负担生殖腺组织库和 ART 的费用，以实现以后的生育。在这篇综述中，讨论了一种通过靶向在肿瘤治疗后存活的内源性干细胞来再生非功能性性腺的替代策略。一种新的多能干细胞群，称为非常小的胚胎样干细胞（VSELs），在成年生殖腺中存在，与晚期迁移的原始生殖细胞在发育上等同，由于其静止状态，它们在肿瘤治疗后存活。然而，干细胞龛在肿瘤治疗后受到损害。移植龛细胞（支持细胞或间充质细胞）可以再生非功能性性腺。这种方法是安全的，已经在老鼠中产生了可育的后代，并可以在生命早期恢复性腺功能，以支持正常生长，以后作为配子的来源。这种新出现的干细胞生物学理解可以避免储存生殖腺组织的需要，并且在肿瘤治疗前已经失去生殖腺组织库的现有癌症幸存者中，生育能力也可能得到恢复。
