Fetal surgical repair with placenta-derived mesenchymal stromal cell engineered patch in a rodent model of myelomeningocele

Chen, Y. Julia; Chung, Karen; Pivetti, Christopher D.; Lankford, Lee; Kabagambe, Sandra; Vanover, Melissa; Becker, James C.; Lee, Chelsey; Tsang, Josephine; Wang, Aijun; Farmer, Diana L.

doi:10.1016/j.jpedsurg.2017.10.040

Cited by 31 publications

(38 citation statements)

References 23 publications

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“…We have shown that a large number of PMSCs can be obtained from a single donor and that they secrete high amounts of neurotrophic factors such as BDNF, HGF, and VEGF (19). In utero transplantation of PMSCs in the ovine SB model has shown pronounced recovery of hind limb motor function, and this effect was confirmed by decreasing the number of apoptotic cells at the site of injury in the retinoic acid-induced rat SB model (23,24,27). To further elucidate the paracrine function of PMSCs, we developed an in vitro apoptotic model and studied their paracrine neuroprotective function.…”

Section: Discussionmentioning

confidence: 94%

Neuroprotective effect of placenta‐derived mesenchymal stromal cells: role of exosomes

et al. 2019

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We have established early‐gestation chorionic villus–derived placenta mesenchymal stromal cells (PMSCs) as a potential treatment for spina bifida (SB), a neural tube defect. Our preclinical studies demonstrated that PMSCs have the potential to cure hind limb paralysis in the fetal lamb model of SB via a paracrine mechanism. PMSCs exhibit neuroprotective function by increasing cell number and neurites, as shown by indirect coculture and direct addition of PMSC‐conditioned medium to the staurosporine‐induced apoptotic human neuroblastoma cell line, SH‐SY5Y. PMSC‐conditioned medium suppressed caspase activity in apoptotic SH‐SY5Y cells, suggesting that PMSC secretome contributes to neuronal survival after injury. As a part of PMSC secretome, PMSC exosomes were isolated and extensively characterized; their addition to apoptotic SH‐SY5Y cells mediated an increase in neurites, suggesting that they exhibit neuroprotective function. Proteomic and RNA sequencing analysis revealed that PMSC exosomes contain several proteins and RNAs involved in neuronal survival and development. Galectin 1 was highly expressed on the surface of PMSCs and PMSC exosomes. Preincubation of exosomes with anti‐galectin 1 antibody decreased their neuroprotective effect, suggesting that PMSC exosomes likely impart their effect via binding of galectin 1 to cells. Future studies will include in‐depth analyses of the role of PMSC exosomes on neuroprotection and their clinical applications.—Kumar, P., Becker, J. C., Gao, K., Carney, R. P., Lankford, L., Keller, B. A., Herout, K., Lam, K. S., Farmer, D. L., Wang, A. Neuroprotective effect of placenta‐derived mesenchymal stromal cells: role of exosomes. FASEB J. 33, 5836–5849 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 94%

Neuroprotective effect of placenta‐derived mesenchymal stromal cells: role of exosomes

et al. 2019

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“…For the past several years, our group has been exploring and establishing stem cell-based regenerative fetal treatments combined with tissue engineering for a variety of congenital disorders. For instance, we have successfully isolated placental mesenchymal stem/stromal cells (PMSCs) from the chorionic villus of early gestation placentas, and developed a PMSC-based fetal treatment for spina bifida (SB) [3,4,[9][10][11][12] . Using the surgically-created fetal ovine SB model, we showed that augmenting in utero surgical repair of SB defects with PMSCs can rescue neurons and cure SB-associated motor function deficits at birth [3,[9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

“…For instance, we have successfully isolated placental mesenchymal stem/stromal cells (PMSCs) from the chorionic villus of early gestation placentas, and developed a PMSC-based fetal treatment for spina bifida (SB) [3,4,[9][10][11][12] . Using the surgically-created fetal ovine SB model, we showed that augmenting in utero surgical repair of SB defects with PMSCs can rescue neurons and cure SB-associated motor function deficits at birth [3,[9][10][11] . However, consistent with numerous other cases in which therapeutic effects were observed using MSCs, the transplanted PMSCs did not persist following transplantation, nor contribute to tissue regeneration by integration [3,[13][14][15][16][17] .…”

Section: Introductionmentioning

confidence: 99%

Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration

Gao¹,

He²,

Kumar³

et al. 2020

WJSC

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BACKGROUND Endothelial colony-forming cells (ECFCs) have been implicated in the process of vascularization, which includes vasculogenesis and angiogenesis. Vasculogenesis is a de novo formation of blood vessels, and is an essential physiological process that occurs during embryonic development and tissue regeneration. Angiogenesis is the growth of new capillaries from pre-existing blood vessels, which is observed both prenatally and postnatally. The placenta is an organ composed of a variety of fetal-derived cells, including ECFCs, and therefore has significant potential as a source of fetal ECFCs for tissue engineering. AIM To investigate the possibility of isolating clonal ECFCs from human early gestation chorionic villi (CV-ECFCs) of the placenta, and assess their potential for tissue engineering. METHODS The early gestation chorionic villus tissue was dissociated by enzyme digestion. Cells expressing CD31 were selected using magnetic-activated cell sorting, and plated in endothelial-specific growth medium. After 2-3 wks in culture, colonies displaying cobblestone-like morphology were manually picked using cloning cylinders. We characterized CV-ECFCs by flow cytometry, immunophenotyping, Data sharing statement: We agree to share the research methods and data in this study to public.

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“…Due to their potential to engraft and to support endogenous neural cells within the host through immunomodulatory and trophic factors, the utility of mesenchymal stem cells has been more thoroughly investigated and has been beneficial in some MMC models of repair. 39,[48][49][50][51][52] The second major finding from our study is the successful establishment of an organotypic model specific to the affected lumbar spinal cord in fetal MMC. Specifically, slice cultures from MMC pups demonstrated robust survival of endogenous cells within fibrin hydrogels for up to 14 days and showed evidence of continued differentiation into mature neuronal phenotypes with robust neurite outgrowth along its periphery.…”

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair

et al. 2020

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Studying how the fetal spinal cord regenerates in an ex vivo model of spina bifida repair may provide insights into the development of new tissue engineering treatment strategies to better optimize neurologic function in affected patients. Here, we developed hydrogel surgical patches designed for prenatal repair of myelomeningocele defects and demonstrated viability of both human and rat neural progenitor donor cells within this three-dimensional scaffold microenvironment. We then established an organotypic slice culture model using transverse lumbar spinal cord slices harvested from retinoic acid–exposed fetal rats to study the effect of fibrin hydrogel patches ex vivo. Based on histology, immunohistochemistry, gene expression, and enzyme-linked immunoabsorbent assays, these experiments demonstrate the biocompatibility of fibrin hydrogel patches on the fetal spinal cord and suggest this organotypic slice culture system as a useful platform for evaluating mechanisms of damage and repair in children with neural tube defects.

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Fetal surgical repair with placenta-derived mesenchymal stromal cell engineered patch in a rodent model of myelomeningocele

Cited by 31 publications

References 23 publications

Neuroprotective effect of placenta‐derived mesenchymal stromal cells: role of exosomes

Neuroprotective effect of placenta‐derived mesenchymal stromal cells: role of exosomes

Clonal isolation of endothelial colony-forming cells from early gestation chorionic villi of human placenta for fetal tissue regeneration

Hydrogel and neural progenitor cell delivery supports organotypic fetal spinal cord development in an ex vivo model of prenatal spina bifida repair

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