In utero treatment of myelomeningocele with placental mesenchymal stromal cells — Selection of an optimal cell line in preparation for clinical trials

Galganski, Laura A.; Kumar, Priyadarsini; Vanover, Melissa; Pivetti, Christopher D.; Anderson, Jamie E.; Lankford, Lee; Paxton, Zachary J.; Chung, Karen; Lee, Chelsey; Hegazi, Mennatalla S; Yamashiro, Kaeli J.; Wang, Aijun; Farmer, Diana L.

doi:10.1016/j.jpedsurg.2019.09.029

Cited by 25 publications

(33 citation statements)

References 39 publications

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“…The characteristics of the included studies, such as type and source of stem cells, animal models and available outcomes, are shown in Table 1 30–55 . Most studies used MSCs (77%, 20/26), with the placenta, amniotic fluid and bone marrow as the source of cells.…”

Section: Resultsmentioning

confidence: 99%

Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta‐analysis

et al. 2021

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Objective We performed a systematic review to summarize the efficacy and safety of in utero stem cells application in preclinical models with myelomeningocele (MMC). Methods The study was registered with PROSPERO (CRD42019160399). We searched MEDLINE, Embase, Web of Science, Scopus and CENTRAL for publications articles on stem cell therapy in animal fetuses with MMC until May 2020. Publication quality was assessed by the SYRCLE's tool. Meta‐analyses were pooled if studies were done in the same animal model providing similar type of stem cell used and outcome measurements. Narrative synthesis was performed for studies that could not be pooled. Results Nineteen and seven studies were included in narrative and quantitative syntheses, respectively. Most used mesenchymal stem cells (MSCs) and primarily involved ovine and rodent models. Both intra‐amniotic injection of allogeneic amniotic fluid (AF)‐MSCs in rat MMC model and the application of human placental (P)‐MSCs to the spinal cord during fetal surgery in MMC ovine model did not compromise fetal survival rates at term (rat model, relative risk [RR] 1.03, 95% CI 0.92–1.16; ovine model, RR 0.94, 95% CI 0.78–1.13). A single intra‐amniotic injection of allogeneic AF‐MSCs into rat MMC model was associated with a higher rate of complete defect coverage compared to saline injection (RR 16.35, 95% CI 3.27–81.79). The incorporation of human P‐MSCs as a therapeutic adjunct to fetal surgery in the ovine MMC model significantly improved sheep locomotor rating scale after birth (mean difference 5.18, 95% CI 3.36–6.99). Conclusions Stem cell application during prenatal period in preclinical animal models is safe and effective.

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Section: Resultsmentioning

confidence: 99%

Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta‐analysis

et al. 2021

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“…The direct and paracrine effects of neural stem cells on the fetal spinal cord remain essentially unknown, 47 and techniques for long-term experiments using spinal cord slice cultures have only recently been described. 14 Since there remains a paucity of well-established biomimetic models that permit effective in vitro screening of fetal spinal cord regeneration, 85 our approach represents a novel, high-throughput platform for evaluating next-generation MMC repair strategies, including stem cells and bioactive molecules, in both the prenatal and postnatal setting. Other stem cell populations, neurotrophins, and growth factors could be screened to better identify the optimal microenvironment to facilitate neural regeneration in this condition.…”

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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“…As previously described, the MMC defect was repaired at 100 days of gestation ±7 days [10]. The fibrinous scar over the spinal cord was removed.…”

Section: Methodsmentioning

confidence: 99%

“…As previous described, the fetal MMC defect was created at 75 days of gestation ±7 days [10]. The skin, paraspinal muscles, vertebral lamina, and dorsal portion of the dura were resected from L1 to L6.…”

Section: Ovine Myelomeningocele Defect Creation Repair and Cesareanmentioning

confidence: 99%

Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study

et al. 2020

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Background: Fetal repair of myelomeningocele (MMC) with placental mesenchymal stromal cells (PMSCs) rescues ambulation in the ovine model up to 48 h postnatally. Outcomes past 48 h are unknown as MMC lambs have not been survived past this timepoint. Objective: We aimed to survive lambs for 6 months following the fetal repair of MMC with PMSCs. Methods: Fetal MMC lambs were repaired with PMSCs. Lambs received either no additional treatment or postnatal bracing and physical therapy (B/PT). Motor function was assessed with the sheep locomotor rating (SLR). Lambs with an SLR of 15 at birth were survived for 6 months or until a decline in SLR less than 15, whichever came first. All lambs underwent a perimortem MRI. Results: The lambs with no postnatal treatment (n = 2) had SLR declines to 7 and 13 at 29 and 65 days, respectively, and were euthanized. These lambs had a spinal angulation of 57° and 47°, respectively. The B/PT lamb (n = 1) survived for 6 months with a sustained SLR of 15 and a lumbar angulation of 42°. Conclusion: Postnatal physical therapy and bracing counteracted the inherent morbidity of the absent paraspinal muscles in the ovine MMC model allowing for survival and maintenance of rescued motor function of the prenatally treated lamb up to 6 months.

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In utero treatment of myelomeningocele with placental mesenchymal stromal cells — Selection of an optimal cell line in preparation for clinical trials

Cited by 25 publications

References 39 publications

Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta‐analysis

Preclinical stem cell therapy in fetuses with myelomeningocele: A systematic review and meta‐analysis

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

Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study

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