Therapeutic application of Sertoli cells for treatment of various diseases

Washburn, Rachel L.; Hibler, Taylor; Thompson, Lea Ann; Kaur, Gurvinder; Dufour, Jannette M.

doi:10.1016/j.semcdb.2021.04.007

Cited by 9 publications

(10 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sertoli cells (SeC) continue to unravel their peculiar effects on a growing number of physiological and pathological conditions [16,25]. In addition to their role in creating a physical barrier in the testes necessary for spermatogenesis, SeC secrete a plethora of factors with trophic and anti-inflammatory effects that have prompted researchers to evaluate the beneficial use of these cells in many pre-clinical models of diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Depending on the experimental model investigated, SeC have shown the ability to protect allogeneic or xenogeneic grafts from immune rejection, or to reduce local inflammation [14,16,26]. Animal models of type 1 or type 2 diabetes, Laron syndrome (dwarfism), Huntington's disease, and others, have been reported to take advantage of the injection of naked or microencapsulated (MC-) SeC [14,25,[27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

“…This is an in vitro study on a murine cell line and a limited number of humanderived healthy and DMD myoblasts that expands an in vivo study in an animal model of DMD [11,12]. The SeC secretory activity results in the production of a cocktail of factors whose formulation is difficult to dissect, the overall effect being not necessarily the sum of the biological effects of single factors [8,25,26]. The identification of a minimal cocktail of factors able to mimic the reported effects of SeC on myoblasts/myotubes should be the aim of further studies.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

et al. 2021

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is an X-linked disease caused by mutations in DMD gene translating in lack of functional dystrophin and resulting in susceptibility of myofibers to rupture during contraction. Inflammation and fibrosis are critical hallmarks of DMD muscles, which undergo progressive degeneration leading to loss of independent ambulation in childhood and death by early adulthood. We reported that intraperitoneal injection of microencapsulated Sertoli cells (SeC) in dystrophic mice translates into recovery of muscle morphology and performance thanks to anti-inflammatory effects and induction of the dystrophin paralogue, utrophin at the muscle level, opening new avenues in the treatment of DMD. The aim of this study is to obtain information about the direct effects of SeC on myoblasts/myotubes, as a necessary step in view of a translational application of SeC-based approaches to DMD. We show that (i) SeC-derived factors stimulate cell proliferation in the early phase of differentiation in C2C12, and human healthy and DMD myoblasts; (ii) SeC delay the expression of differentiation markers in the early phase nevertheless stimulating terminal differentiation in DMD myoblasts; (iii) SeC restrain the fibrogenic potential of fibroblasts, and inhibit myoblast-myofibroblast transdifferentiation; and, (iv) SeC provide functional replacement of dystrophin in preformed DMD myotubes regardless of the mutation by inducing heregulin β1/ErbB2/ERK1/2-dependent utrophin expression. Altogether, these results show that SeC are endowed with promyogenic and antifibrotic effects on dystrophic myoblasts, further supporting their potential use in the treatment of DMD patients. Our data also suggest that SeC-based approaches might be useful in improving the early phase of muscle regeneration, during which myoblasts have to adequately proliferate to replace the damaged muscle mass.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

et al. 2021

View full text Add to dashboard Cite

show abstract

“…It was also found that Sertoli cells are important for adult Leydig cell survival and peritubular myoid cell function ( 16 , 17 ). Additionally, Sertoli cells survive long-term after transplantation as allografts or xenografts to ectopic sites without the use of immunosuppressive drugs ( 18 ). Moreover, Sertoli cells prolong the survival of co-transplanted allogeneic and xenogeneic tissues, such as pancreatic islets, suggesting that Sertoli cells can mimic the immune privileged environment outside of the testis ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, Sertoli cells survive long-term after transplantation as allografts or xenografts to ectopic sites without the use of immunosuppressive drugs ( 18 ). Moreover, Sertoli cells prolong the survival of co-transplanted allogeneic and xenogeneic tissues, such as pancreatic islets, suggesting that Sertoli cells can mimic the immune privileged environment outside of the testis ( 18 ). Sertoli cells also produce several immune modulatory factors (discussed later) that influence the immune response.…”

Section: Introductionmentioning

confidence: 99%

Sertoli Cell Immune Regulation: A Double-Edged Sword

et al. 2022

View full text Add to dashboard Cite

The testis must create and maintain an immune privileged environment to protect maturing germ cells from autoimmune destruction. The establishment of this protective environment is due, at least in part, to Sertoli cells. Sertoli cells line the seminiferous tubules and form the blood-testis barrier (BTB), a barrier between advanced germ cells and the immune system. The BTB compartmentalizes the germ cells and facilitates the appropriate microenvironment necessary for spermatogenesis. Further, Sertoli cells modulate innate and adaptive immune processes through production of immunoregulatory compounds. Sertoli cells, when transplanted ectopically (outside the testis), can also protect transplanted tissue from the recipient’s immune system and reduce immune complications in autoimmune diseases primarily by immune regulation. These properties make Sertoli cells an attractive candidate for inflammatory disease treatments and cell-based therapies. Conversely, the same properties that protect the germ cells also allow the testis to act as a reservoir site for infections. Interestingly, Sertoli cells also have the ability to mount an antimicrobial response, if necessary, as in the case of infections. This review aims to explore how Sertoli cells act as a double-edged sword to both protect germ cells from an autoimmune response and activate innate and adaptive immune responses to fight off infections.

show abstract

Melatonin modulates Nrf2 activity to protect porcine pre‐pubertal Sertoli cells from the abnormal H₂O₂ generation and reductive stress effects of cadmium

Bartolini

Arato

Mancuso

et al. 2022

Journal of Pineal Research

View full text Add to dashboard Cite

Melatonin (MLT) is a cytoprotective agent holding potential to prevent cadmium (Cd) toxicity and its impact in testicular function and fertility. In this study, we explored such potential in porcine pre‐pubertal Sertoli cells (SCs). Cd toxicity resulted in impaired SC viability and function, abnormal cellular H2O2 generation and efflux, and induction of reductive stress by the upregulation of Nrf2 expression and activity, cystine uptake and glutathione biosynthesis, glutathione‐S‐transferase P (GSTP) expression, and protein glutathionylation inhibition. Cd toxicity also stimulated the activity of cellular kinases (MAPK‐ERK1/2 and Akt) and NFkB transcription factor, and cJun expression was increased. MLT produced a potent cytoprotective effect when co‐administered with Cd to SCs; its efficacy and the molecular mechanism behind its cytoprotective function varied according to Cd concentrations. However, a significant restoration of cell viability and function, and of H2O2 levels, was observed both at 5 and 10 μM Cd. Mechanistically, these effects of MLT were associated with a significant reduction of the Cd‐induced activation of Nrf2 and GSTP expression at all Cd concentrations. CAT and MAPK‐ERK1/2 activity upregulation was associated with these effects at 5 μM Cd, whereas glutathione biosynthesis and efflux were involved at 10 μM Cd together with an increased expression of the cystine transporter xCT, of cJun and Akt and NFkB activity. MLT protects SCs from Cd toxicity reducing its H2O2 generation and reductive stress effects. A reduced activity of Nrf2 and the modulation of other molecular players of MLT signaling, provide a mechanistic rational for the cytoprotective effect of this molecule in SCs.

show abstract

Therapeutic application of Sertoli cells for treatment of various diseases

Cited by 9 publications

References 116 publications

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

Sertoli Cell Immune Regulation: A Double-Edged Sword

Melatonin modulates Nrf2 activity to protect porcine pre‐pubertal Sertoli cells from the abnormal H₂O₂ generation and reductive stress effects of cadmium

Contact Info

Product

Resources

About

Therapeutic application of Sertoli cells for treatment of various diseases

Cited by 9 publications

References 116 publications

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts

Sertoli Cell Immune Regulation: A Double-Edged Sword

Melatonin modulates Nrf2 activity to protect porcine pre‐pubertal Sertoli cells from the abnormal H2O2 generation and reductive stress effects of cadmium

Contact Info

Product

Resources

About

Melatonin modulates Nrf2 activity to protect porcine pre‐pubertal Sertoli cells from the abnormal H₂O₂ generation and reductive stress effects of cadmium