論文紹介著者

Zachary Yu-Ching Lin（博士課程 3年）
GCOE　RA
生理学

第一著者名・掲載雑誌・号・掲載年月

Brain P. Hermann／Cell stem cell 11, 715-726, November 2, 2012.

文献の英文表記：著者名・論文の表題・雑誌名・巻・号・ページ・発行年（西暦）

Brain P. Hermann, Meena Sukhwani, Felicity Winkler, Julia N. Pascarella, Karen A. Peters, Yi Sheng, Hanna Valli, Mario Rodriguez, Mohamed Ezzelarab, Gina Dargo, Kim Peterson, Keith Masterson, Cathy Ramsey, Thea Ward, Maura Lienesch, Angie Volk, David K. Cooper, Angus W. Thomoson, Joseph E. Kiss, Maria Cecilla T. Pendo, Gerald P. Schatten, Shoukhrat Mitalipov, and Kyle E. Orwig.
Speramtogonial Stem Cell Transplantation into Rhesus Testes Regenerates Spermatogenesis Producing Functional Sperm.
Cell stem cell 11, 715-726, Novermber 2, 2012

論文解説

Spermatogonial stem cells (SSCs) maintain spermatogenesis throughout a man's life and may have the potential for treating some cases of male infertility, including those caused by receiving chemotherapy before puberty.
The ultimate clinical goal of this research is utilizing SSC transplantation to preserve and restore the fertility of male cancer patients.

They first extract the SSCs from rhesus testis or subcapsular biopsy by using two-step enzymatic digestion, and then performed autologous SSC transplantation with lenti-viral marked reporter into the testes of 18 adult and 5 prepubertal recipient macaques, which were rendered infertile with alkylating chemotherapy, under the observation of ultrasound. After the autologous transplantation, the donor genotype from SSCs with reporter was evident in the ejaculated sperm of 9/12 adult and 3/5 prepubertal recipients after they reached maturity

In order to do a functional assay without bias, they then performed allogeneic transplant of SSC. They suppress the immunity of the recipient first and carried out the allogeneic transplantation. Allogeneic transplant led to donor-recipients chimerism in sperm from 2/6 adult recipients based on the analysis of microsatellite DNA fingerprinting. Ejaculated sperm from one recipient transplanted with allogeneic donor SSCs were injected into 85 rhesus oocytes via intracytoplasmic sperm injection (ICSI). Eighty-one oocytes were fertilized and produced embryos ranging from 4-cells to blastocyst with donor paternal origin confirmed in 7/81 embryos.

This demonstration of functional donor spermatogenesis following SSC transplantation in primate is an important step for clinical application as it might permanently restore the natural fertility of the cancer patient.

Could you add your comments which points in this study are major points of the progress in this field?

I believe the idea of transplanting cryo-preserved SSCs either from the testis and biopsy to the same or different individuals monkey is really a breakthrough in the germ cell research field of primate. This proved that the SSC is able to survived in cryo-preserved condition without compromise its functions as a stem cell. Moreover, to date, the spermatogenesis of primate is still not fully understood, let along the application of reproductive engineering. This paper also shine the light of hope to we primate germ cell researchers that if we can manage to get hold of the SSC, making gene-target animal model is no longer a fantasy anymore.

Plz add the brief illustration of strategy of this study for easy understanding.