PURPOSE: Transamniotic stem cell therapy (TRASCET) with select mesenchymal stem cells (MSCs) has been shown to induce partial or complete skin coverage of spina bifida in rodents. Clinical translation of this emerging therapy hinges on its efficacy in larger animal models. We sought to study TRASCET in a model requiring intra-amniotic injections 60 times larger than those performed in the rat. METHODS: Rabbit fetuses (n = 65) with surgically created spina bifida were divided into three groups. One group (untreated) had no further manipulations. Two groups received volume-matched intra-amniotic injections of either saline or a concentrated suspension of amniotic fluid MSCs (afMSCs) at the time of operation. Infused afMSCs consisted of banked heterologous rabbit afMSCs with mesenchymal identity confirmed by flow cytometry, labeled with green fluorescent protein. Defect coverage at term was blindly categorized only if the presence of a distinctive neoskin was confirmed histologically. Statistical comparisons were by logistic regression and the likelihood ratio test. RESULTS: Among survivors with spina bifida (n = 19), there were statistically significant higher rates of defect coverage (all partial) in the afMSC group when compared with the saline and untreated groups (0-50%; p = 0.022-0.036), with no difference between the saline and untreated groups (p = 1.00). Donor afMSCs were identified locally, though sparsely and not in the neoskin. CONCLUSIONS: Concentrated intra-amniotic injection of amniotic mesenchymal stem cells can induce partial coverage of experimental spina bifida in a leporine model. Transamniotic stem cell therapy may become a feasible strategy in the prenatal management of spina bifida. LEVEL OF EVIDENCE: N/A (animal and laboratory study).
PURPOSE: Transamniotic stem cell therapy (TRASCET) with select mesenchymal stem cells (MSCs) has been shown to induce partial or complete skin coverage of spina bifida in rodents. Clinical translation of this emerging therapy hinges on its efficacy in larger animal models. We sought to study TRASCET in a model requiring intra-amniotic injections 60 times larger than those performed in the rat. METHODS:Rabbit fetuses (n = 65) with surgically created spina bifida were divided into three groups. One group (untreated) had no further manipulations. Two groups received volume-matched intra-amniotic injections of either saline or a concentrated suspension of amniotic fluid MSCs (afMSCs) at the time of operation. Infused afMSCs consisted of banked heterologous rabbit afMSCs with mesenchymal identity confirmed by flow cytometry, labeled with green fluorescent protein. Defect coverage at term was blindly categorized only if the presence of a distinctive neoskin was confirmed histologically. Statistical comparisons were by logistic regression and the likelihood ratio test. RESULTS: Among survivors with spina bifida (n = 19), there were statistically significant higher rates of defect coverage (all partial) in the afMSC group when compared with the saline and untreated groups (0-50%; p = 0.022-0.036), with no difference between the saline and untreated groups (p = 1.00). Donor afMSCs were identified locally, though sparsely and not in the neoskin. CONCLUSIONS: Concentrated intra-amniotic injection of amniotic mesenchymal stem cells can induce partial coverage of experimental spina bifida in a leporine model. Transamniotic stem cell therapy may become a feasible strategy in the prenatal management of spina bifida. LEVEL OF EVIDENCE: N/A (animal and laboratory study).
Authors: Sarah C Stokes; Kaeli J Yamashiro; Melissa A Vanover; Laura A Galganski; Jordan E Jackson; Christina M Theodorou; Christopher D Pivetti; Diana Lee Farmer; Aijun Wang Journal: Biomed Res Int Date: 2021-08-13 Impact factor: 3.411
Authors: Yada Kunpalin; Sindhu Subramaniam; Silvia Perin; Mattia F M Gerli; Jan Bosteels; Sebastien Ourselin; Jan Deprest; Paolo De Coppi; Anna L David Journal: Prenat Diagn Date: 2021-01-11 Impact factor: 3.242
Authors: Nathan Maassel; James Farrelly; Daniel Coman; Mollie Freedman-Weiss; Samantha Ahle; Sarah Ullrich; Nicholas Yung; Fahmeed Hyder; David Stitelman Journal: PLoS One Date: 2021-06-30 Impact factor: 3.240
Authors: Sarah C Stokes; Jordan E Jackson; Christina M Theodorou; Christopher D Pivetti; Priyadarsini Kumar; Kaeli J Yamashiro; Aijun Wang; Diana L Farmer Journal: Fetal Diagn Ther Date: 2021-06-10 Impact factor: 2.208