Does Bone Marrow–derived Mesenchymal Stem Cell Transfusion Prevent Antisperm Antibody Production After Traumatic Testis Rupture?

doi:10.1016/j.urology.2014.03.009

Urology

Volume 84, Issue 1, July 2014, Pages 82-86

https://doi.org/10.1016/j.urology.2014.03.009 Get rights and content

Objective

To determine whether transfusion of mesenchymal stem cells (MSCs) could prevent humoral immune response and autoimmunization against sperms after traumatic testis rupture.

Methods

Immunomodulatory properties of MSCs have been evaluated by a prospective cohort on 50 adult BALB/c mice. In each interventional arms of study, controlled testis rupture and surgical repair were exerted. In addition to tissue repair, single dose of 5 × 10⁵ MSCs labeled by green fluorescent protein was delivered intravenously to 20 cases (cell therapy group). After euthanizing, seroconversion of antisperm antibody (ASA) was compared between 2 interventional groups as response of humoral immune system. Lung and testis tissues were examined for green fluorescent protein–positive cells to assess whether presence of stem cells is correlated with seroconversion rates.

Results

Six cases had been lost during the study. Fourteen of 16 mice in cell therapy control group formed ASA (87.5%) but 6 of 18 mice (33.3%) in cell therapy group were immunized and formed ASA (P = .002). Transplanted cells were traced in lungs of 55% (n = 10) of cell therapy group and none were found in trauma site. Small volume of mice blood was our main limitation to trace seroconversion or quantitative measurement of ASA in each case.

Conclusion

In this in vivo model of autoimmune infertility, bone marrow–derived MSC transfusion showed immunosuppressive effects on antibody production. Considering immunomodulatory properties of MSCs even in allogeneic settings, novel clinical application should be investigated further.

Section snippets

Subjects and Methods

The study was approved by local ethics committee (Trauma Research Center, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran). The chemicals consumed in this study were purchased from Sigma-Aldrich (Pool, UK) unless stated otherwise. Animal surgical procedure and maintenance was carried out under supervision of Veterinary Medicine Faculty of University of Tehran guidelines, and ethical approval was obtained from the ethics scrutiny committee before conduction of the experiments.

Results

Six cases were lost during the study: 4 because of anesthesia recovery failure (3 from group 1 and 1 from group 2) and 2 other died during 3 first postoperative days, 1 mouse each from group 1 and 2.

All 10 negative control mice (group 0_a,b) were ASA negative and negative for GFP-stained cells regarding lung and testis tissues. ASA production rate was 87.5% (14 of 16) in cell therapy control mice (group1) but only 6 of 18 mice (33.3%) that received MSCs (group 2) had ASA in their serum (P

Comment

During the past few years, a body of evidence is growing on immunomodulatory effects of MSCs,8, 17, 18, 19 which were first discovered as a suppressing effect on T-cell proliferation by means of soluble factors that refrains the pathway somewhere before the IL2 action, which are best reviewed in Abdi et al work (2008) that are believed to include transforming growth factor beta family and IL10. Besides, it has been shown that MSCs lack of costimulatory surface antigen in interaction with T-cell

Conclusion

This study yields that, even in an allogeneic setting, bone marrow–derived MSC transfusion exerted immunosuppressive effects on antibody production in an in vivo model. These results may facilitate the current attempts to reveal the immunomodulatory pathways of MSCs and help establishing a novel clinical application for MSCs in future.

Acknowledgments

Authors wish to thank Dr. Mohammad Ghodsi (Sina Trauma and Surgery Research Center) and Mazdak Salavati for reviewing the manuscript, and staff of Sina Hospital Pathology Laboratory for their kind cooperation, especially Dr. Moradi and Mrs. Nikie.

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: Financial Disclosure: The authors declare that they have no relevant financial interests.

: Funding Support: This work was funded by the kind contribution of Dr. Naser Ahmadbeigi (Sabz Biotech Ltd) and Tehran University Trauma Research Center.

View full text

InfertilityDoes Bone Marrow–derived Mesenchymal Stem Cell Transfusion Prevent Antisperm Antibody Production After Traumatic Testis Rupture?

Objective

Methods

Results

Conclusion

Section snippets

Subjects and Methods

Results

Comment

Conclusion

Acknowledgments

Fertil Steril

Cytotherapy

Blood

Trends Immunol

Blood

Exp Hematol

Cytotherapy

J Pediatr Surg

Exp Hematol

Blood

Transpl Immunol

Blood

Exp Cell Res

Stumpfes Hodentrauma-wann konservative, wann operative Behandlung? blunt testicular injury—conservative or surgical treatment?

Aktuelle Urol

Infertility
Does Bone Marrow–derived Mesenchymal Stem Cell Transfusion Prevent Antisperm Antibody Production After Traumatic Testis Rupture?