Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele

Kabagambe, Sandra; Keller, B; Becker, James C.; Goodman, Libby; Pivetti, Christopher D.; Lankford, Lee; Chung, Karen; Lee, Chelsey; Chen, Y. Julia; Kumar, Priyadarsini; Vanover, Melissa; Wang, Aijun; Farmer, Diana L.

doi:10.1016/j.jpedsurg.2017.10.032

Cited by 41 publications

(53 citation statements)

References 28 publications

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“…Intra-amniotic injections of amniotic or placental fluid derived mesenchymal stem cells induced partial or complete coverage of MMC defects and a reduction in Chiari II formation in a retinoic acideinduced rat model of MMC. 24,[45][46][47] These promising results demonstrate the potential of tissue-engineered approaches compared with traditional open repair approaches for MMC repair.…”

Section: Discussionmentioning

confidence: 85%

“…16 Current research strategies have either incorporated biomaterial patches as a means to cover MMC defects for the duration of the pregnancy or used a conventional laparoscopic repair using multiple trocar insertion sites. [17][18][19][20][21][22][23][24] Despite promising preliminary results, these approaches are still considered experimental and are done relatively late in gestation, at 22-to 24-wk gestation. Moreover, they are associated with chorioamniotic membrane complications, require two to three trocar insertion sites that create multiple membrane violations/fixations, require a significant operative time with CO 2 insufflation that can lead to significant hypercarbia and acidosis, and fetal exposure to inhalational anesthetic agents used for the mother.…”

Section: Introductionmentioning

confidence: 99%

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An Injectable Reverse Thermal Gel for Minimally Invasive Coverage of Mouse Myelomeningocele

Bardill

Williams

Shabeka

et al. 2019

Journal of Surgical Research

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Background: Myelomeningocele (MMC) results in lifelong neurologic and functional deficits. Currently, prenatal repair of MMC closes the defect, resulting in a 50% reduction in postnatal ventriculoperitoneal shunting. However, this invasive fetal surgery is associated with significant morbidities to mother and baby. We have pioneered a novel reverse thermal gel (RTG) to cover MMC defects in a minimally invasive manner. Here, we test in-vitro RTG long-term stability in amniotic fluid and in vivo application in the Grainy head-like 3 (Grhl3) mouse MMC model. Materials and methods: RTG stability in amniotic fluid (in-vitro) was monitored for 6 mo and measured using gel permeation chromatography and solutionegel transition temperature (lower critical solution temperature). E16.5 Grhl3 mouse fetuses were injected with the RTG or saline and harvested on E19.5. Tissue was assessed for RTG coverage of the gross defect and inflammatory response by immunohistochemistry for macrophages. Results: Polymer backbone molecular weight and lower critical solution temperature remain stable in amniotic fluid after 6 mo. Needle injection over the MMC of Grhl3 fetuses successfully forms a stable gel that covers the entire defect. On harvest, some animals demonstrate >50% RTG coverage. RTG injection is not associated with inflammation. Conclusions: Our results demonstrate that the RTG is a promising candidate for a minimally invasive approach to patch MMC. We are now poised to test our RTG patch in the large preclinical ovine model used to evaluate prenatal repair of MMC.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

An Injectable Reverse Thermal Gel for Minimally Invasive Coverage of Mouse Myelomeningocele

Bardill

Williams

Shabeka

et al. 2019

Journal of Surgical Research

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“…Despite several reports of differentiation potential to various cell lineages in vitro and in vivo , their regenerative potential is predominantly executed by the trophic factors secreted by MSCs via a paracrine mechanism (1). MSCs can be isolated from various sources, and our lab has primarily focused on PMSCs isolated from discarded early‐gestation chorionic villus tissue and its application for treatment of myelomeningocele (16, 23, 24, 27). 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).…”

Section: Discussionmentioning

confidence: 99%

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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“…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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Placental mesenchymal stromal cells seeded on clinical grade extracellular matrix improve ambulation in ovine myelomeningocele

Cited by 41 publications

References 28 publications

An Injectable Reverse Thermal Gel for Minimally Invasive Coverage of Mouse Myelomeningocele

An Injectable Reverse Thermal Gel for Minimally Invasive Coverage of Mouse Myelomeningocele

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

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