Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration

Arun Sharma, Matthew I. Bury, Natalie J. Fuller, Andrew J. Marks, David M. Kollhoff, Manoj V. Rao, Partha V. Hota, Derek John Matoka, Seby L. Edassery, Hatim Thaker, John F Sarwark, Joseph A Janicki, Guillermo Antonio Ameer, Earl Y Cheng

Research output: Contribution to journalArticle

  • 45 Citations

Abstract

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we 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 unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34+ hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34+ grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

LanguageEnglish (US)
Pages4003-4008
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number10
DOIs
StatePublished - Mar 5 2013

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Spinal Dysraphism
Bone Marrow Cells
Regeneration
Urinary Bladder
Stem Cells
Hematopoietic Stem Cells
Mesenchymal Stromal Cells
Population
Neurogenic Urinary Bladder
Peripheral Nerves
Smooth Muscle
Tissue Donors
Nerve Tissue
Meningomyelocele
Urothelium
Tissue Engineering
Standard of Care
Growth
Bone Marrow
Transplants

Keywords

  • Angiogenesis
  • Biocompatible polymer
  • Cell-seeded matrix
  • Multipotent
  • Organ repair

ASJC Scopus subject areas

  • General

Cite this

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title = "Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration",
abstract = "Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we 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 unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34+ hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34+ grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.",
keywords = "Angiogenesis, Biocompatible polymer, Cell-seeded matrix, Multipotent, Organ repair",
author = "Arun Sharma and Bury, {Matthew I.} and Fuller, {Natalie J.} and Marks, {Andrew J.} and Kollhoff, {David M.} and Rao, {Manoj V.} and Hota, {Partha V.} and Matoka, {Derek John} and Edassery, {Seby L.} and Hatim Thaker and Sarwark, {John F} and Janicki, {Joseph A} and Ameer, {Guillermo Antonio} and Cheng, {Earl Y}",
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Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration. / Sharma, Arun; Bury, Matthew I.; Fuller, Natalie J.; Marks, Andrew J.; Kollhoff, David M.; Rao, Manoj V.; Hota, Partha V.; Matoka, Derek John; Edassery, Seby L.; Thaker, Hatim; Sarwark, John F; Janicki, Joseph A; Ameer, Guillermo Antonio; Cheng, Earl Y.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 10, 05.03.2013, p. 4003-4008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cotransplantation with specific populations of spina bifida bone marrow stem/progenitor cells enhances urinary bladder regeneration

AU - Sharma, Arun

AU - Bury, Matthew I.

AU - Fuller, Natalie J.

AU - Marks, Andrew J.

AU - Kollhoff, David M.

AU - Rao, Manoj V.

AU - Hota, Partha V.

AU - Matoka, Derek John

AU - Edassery, Seby L.

AU - Thaker, Hatim

AU - Sarwark, John F

AU - Janicki, Joseph A

AU - Ameer, Guillermo Antonio

AU - Cheng, Earl Y

PY - 2013/3/5

Y1 - 2013/3/5

N2 - Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we 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 unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34+ hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34+ grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

AB - Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we 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 unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34+ hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34+ grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

KW - Angiogenesis

KW - Biocompatible polymer

KW - Cell-seeded matrix

KW - Multipotent

KW - Organ repair

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U2 - 10.1073/pnas.1220764110

DO - 10.1073/pnas.1220764110

M3 - Article

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SP - 4003

EP - 4008

JO - Proceedings of the National Academy of Sciences of the United States of America

T2 - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

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