Spina bifida (SB) is the most common disabling birth defect in the United States. Patients with SB typically possess a neurogenic bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention is the current end-stage standard of care in which to treat the neurogenic bladder, it is associated with many complications. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when utilizing populations of cells from the patient.
In a publication to appear in Proceedings of the National Academy of Sciences of the United States of America (PNAS), Arun Sharma, Earl Cheng and colleagues from Northwestern University, Loyola University, Rush University and Ann & Robert H. Lurie Children’s Hospital of Chicago demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a novel and alternative means to current bladder regeneration approaches.
Primitive multipotent bone marrow CD34+ hematopoietic stem/progenitor cells (HSPCs) have the potential to differentiate into various cellular constituents of blood under appropriate environmental stimuli. In addition, they have the unique ability to induce either angiogenesis or vasculogenesis, and thus could provide a means for tissue revascularization. Multipotent mesenchymal stem cells (MSCs) have demonstrated the ability to differentiate into well characterized cell types while also providing compensatory factors to damaged tissue by aiding in tissue repair within in vivo settings.
Within this study, data demonstrate that SB BM MSCs are not affected by pathologies associated with SB and can respond similarly to normal, adult and pediatric control counterparts under in vitro and bladder regenerative conditions. Secondly, the study also demonstrates that donor-matched SB MSCs with CD34+ HSPCs leads to superior blood vessel formation and robust urothelium regeneration in vivo. Lastly, the combination of MSCs and CD34+ HSPCs provides a pro-neural growth environment that allows for the in-growth of peripheral nerves into areas of bladder regeneration. Hence, SB BM stem/progenitor cells provide distinct advantages over native bladder cells from SB patients as MSC/CD34+ scaffold composites may provide an alternative solution to current surgical bladder augmentation strategies.
“The utility of autologous sources of bone marrow stem/progenitor cells in a bladder regenerative setting provides a novel and alternative means to combat the current issues that affect bladder tissue engineering strategies,” explains Sharma, the senior and corresponding author of the publication. “This proof of concept study further demonstrates that specific populations of bone marrow cells can enhance bladder regeneration for a wide range of patients in need of bladder replacement measures. These groups could potentially include those suffering from bladder cancer or trauma as well as other debilitating bladder diseases.”
This work was supported in part by the Excellence in Academic Medicine grant funded through the Illinois Department of Healthcare and Family Services. Arun K. Sharma, PhD is Director of Pediatric Urological Regenerative Medicine at Lurie Children's Division of Pediatric Urology; Research assistant professor of Urology at Northwestern University Feinberg School of Medicine; a member of the Institute for BioNanotechnology in Medicine at Northwestern University; and a member of the Developmental Biology Program of Ann & Robert H. Lurie Children’s Hospital of Chicago Research Center.
Full citation: Sharma AK, Bury MI, Fuller NJ, Marks AJ, Kollhoff DM, Rao MV, Hota PV, Matoka DJ, Edassery SL, Thaker H, Sarwark JF, Janicki JA, Ameer GA, Cheng EY. Co-transplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration. Proceedings of the National Academy of Sciences of the United States of America, in press.
Ann & Robert H. Lurie Children's Hospital of Chicago Research Center is the research arm of Ann & Robert H. Lurie Children's Hospital of Chicago, the pediatric teaching hospital for Northwestern University Feinberg School of Medicine. The research center is also one of the interdisciplinary research centers and institutes of the Feinberg School, where principal investigators who are part of the research center are full-time faculty members.