RESUMEN
Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat life-threatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.
Asunto(s)
Células de Sertoli/inmunología , Terapia GenéticaRESUMEN
Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat life-threatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.(AU)
Asunto(s)
Células de Sertoli/inmunología , Terapia GenéticaRESUMEN
The blood-testis barrier (BTB) is known for its ability to create an immune privilege site in the seminiferous epithelium, but less is known of the blood-epididymal barrier (BEB). It is already established that the fully functional BTB and BEB are much more complex and consist of anatomical/physical (tight junctions, basolateral and apical membranes), physiological and immunological components, which are all necessary to make a functioning barrier in the testis and epididymis. However, comparative data for metazoans suggest that an effective Sertoli cell barrier is not entirely necessary for the development of germ cells during spermatogenesis or that our knowledge about the barrier structure/function in metazoans is still immature. This chapter compares the unique barrier formed by the Sertoli cells of the testis to that formed by the apical junctional complexes of the epididymal epithelium.
Asunto(s)
Barrera Hematotesticular/inmunología , Epidídimo/inmunología , Testículo/inmunología , Animales , Barrera Hematotesticular/anatomía & histología , Barrera Hematotesticular/fisiología , Diferenciación Celular , Permeabilidad de la Membrana Celular , Epidídimo/anatomía & histología , Epidídimo/fisiología , Supervivencia de Injerto/inmunología , Humanos , Tolerancia Inmunológica , Masculino , Filogenia , Epitelio Seminífero/inmunología , Epitelio Seminífero/fisiología , Células de Sertoli/inmunología , Células de Sertoli/fisiología , Células de Sertoli/ultraestructura , Maduración del Esperma , Espermatogénesis , Espermatozoides/inmunología , Espermatozoides/fisiología , Testículo/anatomía & histología , Testículo/fisiología , Uniones Estrechas/inmunología , Uniones Estrechas/fisiología , Uniones Estrechas/ultraestructura , Inmunología del TrasplanteRESUMEN
Transplantation of spermatogonial stem cells (SSCs), the male germline stem cells, in experimental animal models has been successfully used to study mechanisms involved in SSC self-renewal and to restore fertility. However, there are still many challenges associated with understanding the recipient immune response for SSCs use in clinical therapies. Here, we have undertaken a detailed structural study of macrophages elicited by SSCs transplantation in mice using both high-resolution light microscopy (HRLM) and transmission electron microscopy (TEM). We demonstrate that SSCs transplantation elicits a rapid and potent recruitment of macrophages into the seminiferous epithelium (SE). Infiltrating macrophages were derived from differentiation of peritubular monocyte-like cells into typical activated macrophages, which actively migrate through the SE, accumulate in the tubule lumen, and direct phagocytosis of differentiating germ cells and spermatozoa. Quantitative TEM analyses revealed increased formation of lipid bodies (LBs), organelles recognized as intracellular platforms for synthesis of inflammatory mediators and key markers of macrophage activation, within both infiltrating macrophages and Sertoli cells. LBs significantly increased in number and size in parallel to the augmented macrophage migration during different times post-transplantation. Our findings suggest that LBs may be involved with immunomodulatory mechanisms regulating the seminiferous tubule niche after SSC transplantation.
Asunto(s)
Microscopía Electrónica de Transmisión/métodos , Epitelio Seminífero/ultraestructura , Túbulos Seminíferos/ultraestructura , Células de Sertoli/ultraestructura , Espermatogonias/ultraestructura , Trasplante de Células Madre/métodos , Células Madre/inmunología , Animales , Recuento de Células , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Citocinas/biosíntesis , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/ultraestructura , Masculino , Ratones , Monocitos/citología , Monocitos/inmunología , Monocitos/ultraestructura , Orgánulos/inmunología , Orgánulos/ultraestructura , Fagocitosis/inmunología , Epitelio Seminífero/inmunología , Túbulos Seminíferos/inmunología , Células de Sertoli/inmunología , Espermatogénesis , Espermatogonias/citología , Espermatogonias/inmunología , Espermatogonias/trasplante , Células Madre/citología , Factores de TiempoAsunto(s)
Ensayos Clínicos como Asunto/normas , Diabetes Mellitus/patología , Diabetes Mellitus/terapia , Ética Médica , Trasplante de Islotes Pancreáticos/normas , Porcinos , Trasplante Heterólogo/normas , Adolescente , Animales , Ensayos Clínicos como Asunto/legislación & jurisprudencia , Diabetes Mellitus/inmunología , Diabetes Mellitus/metabolismo , Experimentación Humana , Humanos , Terapia de Inmunosupresión , Trasplante de Islotes Pancreáticos/efectos adversos , Trasplante de Islotes Pancreáticos/inmunología , Trasplante de Islotes Pancreáticos/legislación & jurisprudencia , Masculino , México , Guías de Práctica Clínica como Asunto , Células de Sertoli/inmunología , Células de Sertoli/trasplante , Trasplante Heterólogo/efectos adversos , Trasplante Heterólogo/inmunología , Trasplante Heterólogo/legislación & jurisprudencia , Estados Unidos , United States Food and Drug AdministrationRESUMEN
PROBLEM: The presence of cell adhesion molecules (CAMs) in Sertoli cells has not been explored extensively. The expression of CAMs involved in cell-matrix and cell-to-cell interactions in Sertoli cell cultures was examined. METHOD OF STUDY: Immunohistochemical and Western blot techniques were applied to rat Sertoli cell cultures using specific antibodies to alpha 3, alpha 5, and alpha 6 integrin subunits; NCAM; and cadherins. RESULTS: Expression of alpha 3 and alpha 6 integrin subunits (mainly laminin receptors) and lack of expression of alpha 5 integrin subunit (fibronectin receptor) was observed in Sertoli cells by immunohistochemistry. These cells also expressed neural CAM (NCAM) and N-cadherin. By Western blot analysis, Sertoli cell extracts reacted with antibodies to alpha 3 integrin subunit revealed a band approximately 130 kDa, whereas no expression of alpha 5 integrin subunit was detected. Cell extracts incubated with antibodies to pan cadherin exhibited a band approximately 120 kDa, whereas bands of 180, 140, and 120 kDa were observed with antibodies to NCAM. CONCLUSION: New data about the expression of receptors for extracellular matrix proteins (alpha 3 and alpha 6 integrin subunits) as well as cell-to-cell adhesion molecules (NCAM and cadherins) are reported in rat Sertoli cell cultures.