Application potential of bone marrow mesenchymal stem cell (BMSCs) based tissue-engineering for spinal cord defect repair in rat fetuses with spina bifida aperta.

Xiaoshuai Li,Bo Liu,Weilin Wang,Wei Ma,Hui Li,Jiaoning Miao,Dong An,Xiaowei Wei,Songying Cao,Henan Zhang,Guifeng Zhao,Di Wu,Hui Gu,Zhengwei Yuan,Qiushi Wang

doi:10.1007/s10856-016-5684-7

Xiaoshuai Li, Bo Liu + Show 13 more

Open Access

https://doi.org/10.1007/s10856-016-5684-7

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Abstract

Spina bifida aperta are complex congenital malformations resulting from failure of fusion in the spinal neural tube during embryogenesis. Despite surgical repair of the defect, most patients who survive with spina bifida aperta have a multiple system handicap due to neuron deficiency of the defective spinal cord. Tissue engineering has emerged as a novel treatment for replacement of lost tissue. This study evaluated the prenatal surgical approach of transplanting a chitosan–gelatin scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in the healing the defective spinal cord of rat fetuses with retinoic acid induced spina bifida aperta. Scaffold characterisation revealed the porous structure, organic and amorphous content. This biomaterial promoted the adhesion, spreading and in vitro viability of the BMSCs. After transplantation of the scaffold combined with BMSCs, the defective region of spinal cord in rat fetuses with spina bifida aperta at E20 decreased obviously under stereomicroscopy, and the skin defect almost closed in many fetuses. The transplanted BMSCs in chitosan–gelatin scaffold survived, grew and expressed markers of neural stem cells and neurons in the defective spinal cord. In addition, the biomaterial presented high biocompatibility and slow biodegradation in vivo. In conclusion, prenatal transplantation of the scaffold combined with BMSCs could treat spinal cord defect in fetuses with spina bifida aperta by the regeneration of neurons and repairmen of defective region.

Highlights

Neural tube defects (NTDs) are common congenital malformation
This study evaluated the prenatal surgical approach of transplanting a chitosan–gelatin scaffold seeded with bone marrow mesenchymal stem cells (BMSCs) in the healing the defective spinal cord of rat fetuses with retinoic acid induced spina bifida aperta
The results found that the defective region of spinal cord in rat fetuses with spina bifida aperta at E20 decreased obviously after transplantation of the scaffold combined with BMSCs, and the skin defect almost closed compared with the fetus without transplantation under stereomicroscopy (Fig. 5a, c)

Summary

Introduction

Neural tube defects (NTDs) are common congenital malformation. Spina bifida and anencephaly are the most common and severe forms of NTD affecting about 1 in 2000 live births worldwide [1]. Neural tube defects treatment has no breakthrough progress, in addition, Hydrocephalus, lower limb dysfunction and urinary incontinence is still serious postoperative complications [3]. Fetal cellular therapy is a treatment option for a variety of birth defects, and it has been employed in the treatment of congenital haematologic disorders and immunodeficiency disease [4,5,6], and in experimental foetal lamb model of myelomeningocele (MMC) [7]. Bone marrow-derived mesenchymal stem cells (BMSCs) have the capacity to self-renew, easy isolation, implanted less adverse reaction and multipotent differentiation potential such as skeletal muscle, lung, vascular, neuron, astrocyte, 77 Page 2 of 11

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