Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury  

作　　者：Ting-Ting Cao Huan Chen Mao Pang Si-Si Xu Hui-Quan Wen Bin Liu Li-Min Rong Mang-Mang Li 

机构地区：[1]Department of Cell Biology,School of Basic Medical Sciences,Southern Medical University,Guangzhou,Guangdong Province,China [2]Department of Spine Surgery,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong Province,China [3]Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery,Guangzhou,Guangdong Province,China [4]Guangdong Provincial Center for Quality Control of Minimally Invasive Spine Surgery,Guangzhou,Guangdong Province,China [5]Department of Radiology,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2022年第8期1785-1794,共10页中国神经再生研究（英文版）

基　　金：supported by the National Key Research and Development Program of China,No.2017YFA0105401(to LMR);the National Natural Science Foundation of China,Nos.31671420 and 81602482(to MML);a grant from the Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases.

摘　　要：Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10^(6) hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10^(6) cells/kg),medium(1×10^(6) cells/kg)and high(4×10^(6) cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10^(6) hUC-MSCs/kg is an alternative approach for treating subacute SCI.

关 键 词：effective dose human umbilical cord mesenchymal stem cells intrathecal implantation ion channels neurotransmitter receptors spinal cord injury subacute spinal cord injury γ-aminobutyric acid type A(GABA_(A))receptors 

分 类 号：R651.2[医药卫生—外科学]