Sensory neuron differentiation potential of in utero mesenchymal stem cell transplantation in rat fetuses with spina bifida aperta

Ma, Wei; Wei, Xiaowei; Gu, Hui; Li, Hui; Guan, Kaoping; Liú, Dan; Chen, Lizhu; Cao, Songying; An, Dong; Zhang, Henan; Huang, Tzung-Chi; Jiang, Miao; Zhao, Guifeng; Wu, Di; Liu, Bo; Wang, Weilin; Yuan, Zhengwei

doi:10.1002/bdra.23401

Cited by 12 publications

(16 citation statements)

References 43 publications

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“…As deficiencies resulting from NTDs are found in the neural tissue, skin, muscle, and skeleton, BMSCs with multi-lineage differentiation potential could facilitate the repair of multiple tissue damages resulting from NTDs. Indeed, our previous studies have shown that BMSCs directly injected into the fetal spinal column differentiated into nerve and muscle cells, secreted growth factors, and reduced neural apoptosis 20 – 24 . Nevertheless, direct cell injection into neural tissue is not only a technical challenge but also poses a risk of trauma to the fetus.…”

Section: Introductionmentioning

confidence: 99%

Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration

Wei

et al. 2020

Cell Death Dis

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Neural tube defects (NTDs) lead to prenatal mortality and lifelong morbidity. Currently, surgical closure of NTD lesions results in limited functional recovery. We previously suggested that nerve regeneration was critical for NTD therapy. Here, we report that transamniotic bone marrow-derived mesenchymal stem cell (BMSC) therapy for NTDs during early development may achieve beneficial functional recovery. In our ex vivo rat embryonic NTD model, BMSCs injected into the amniotic cavity spontaneously migrated into the defective neural tissue. Hepatocyte growth factor and its receptor c-MET were found to play critical roles in this NTD lesion-specific migration. Using the in vivo rat fetal NTD model, we further discovered that the engrafted BMSCs specifically differentiated into the cell types of the defective tissue, including skin and different types of neurons in situ. BMSC treatment triggered skin repair in fetuses, leading to a 29.9 ± 5.6% reduction in the skin lesion area. The electrophysiological functional recovery assay revealed a decreased latency and increased motor-evoked potential amplitude in the BMSC-treated fetuses. Based on these positive outcomes, ease of operation, and reduced trauma to the mother and fetus, we propose that transamniotic BMSC administration could be a new effective therapy for NTDs.

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Section: Introductionmentioning

confidence: 99%

Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration

Wei

et al. 2020

Cell Death Dis

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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%

“…In small animal models, injection of adult rat BM‐MSCs at E16 into the spinal cord of retinoic acid generated fetal rats with MMC, was associated with a reduction in spinal cord cell death assessed by TUNEL analysis at E20 (death cells; 4.8 ± 0.3% vs. 8.9 ± 0.6%, p < 0.05), 34 and an increase in the number of sensory neurons in the dorsal root ganglion (33.4 ± 1.9% vs. 25.3 ± 1.6%, p < 0.01) 35 . The intervention also improved corticospinal tract communication to the anterior tibialis muscle, demonstrated by a rise in motor evoked potentials (0.26 ± 0.02 mV vs. 0.18 ± 0.02 mV, p < 0.05) and a shorter latency period (22.8 ± 0.3 ms vs. 25.4 ± 0.8 ms, p < 0.05) 38 …”

Section: Efficacy Of Treatmentmentioning

confidence: 97%

“…Risk of bias of the included studies is shown in Figure 2 Li, 2014 (34) Adult Wistar rat Ma, 2015 (35) Adult Wistar rat Li, 2016 (36) Adult Wistar rat Wei, 2020a (37) Adult Wistar rat Wei, 2020b (38) Adult Wistar rat Dionigi, 2015a (39) Normal Lewis rat fetus Dionigi, 2015b (40) Normal Lewis rat fetus Feng, 2016 (41) Normal Lewis rat fetus Turner, 2013 (48) Lewis rat fetuses with NTDs…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

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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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“…Due to the multipotentiality of MSCs, they can possibly be used to treat a variety of conditions. In rats, MSCs injected into the spinal cord of fetuses, which were induced to have spina bifida by the administration of retinoic acid, engrafted and expressed markers of motor neurons, neurons, sensory neurons, and neural precursor cells while inducing the expression of neurotrophic factors from the surrounding tissue [44, 45]. Transplanted MSCs also showed improved bone mineralization in mouse models of osteogenesis imperfecta and could be detected in a human patient suffering from the same disease after transplantation, indicating their potential as a possible therapeutic avenue for osteogenesis imperfecta [46, 47].…”

Section: In Utero Stem Cell Transplantation (Table 1)mentioning

confidence: 99%

In Utero Stem Cell Transplantation: Potential Therapeutic Application for Muscle Diseases

Chowdhury

Asakura

2017

Stem Cells International

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Muscular dystrophies, myopathies, and traumatic muscle injury and loss encompass a large group of conditions that currently have no cure. Myoblast transplantations have been investigated as potential cures for these conditions for decades. However, current techniques lack the ability to generate cell numbers required to produce any therapeutic benefit. In utero stem cell transplantation into embryos has been studied for many years mainly in the context of hematopoietic cells and has shown to have experimental advantages and therapeutic applications. Moreover, patient-derived cells can be used for experimental transplantation into nonhuman animal embryos via in utero injection as the immune response is absent at such early stages of development. We therefore propose in utero transplantation as a potential method to generate patient-derived humanized skeletal muscle as well as muscle stem cells in animals for therapeutic purposes as well as patient-specific drug screening.

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Sensory neuron differentiation potential of in utero mesenchymal stem cell transplantation in rat fetuses with spina bifida aperta

Cited by 12 publications

References 43 publications

Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration

Transamniotic mesenchymal stem cell therapy for neural tube defects preserves neural function through lesion-specific engraftment and regeneration

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

In Utero Stem Cell Transplantation: Potential Therapeutic Application for Muscle Diseases

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