PMID- 35017439
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220225
IS  - 1673-5374 (Print)
IS  - 1876-7958 (Electronic)
IS  - 1673-5374 (Linking)
VI  - 17
IP  - 8
DP  - 2022 Aug
TI  - Dose optimization of intrathecal administration of human umbilical cord 
      mesenchymal stem cells for the treatment of subacute incomplete spinal cord 
      injury.
PG  - 1785-1794
LID - 10.4103/1673-5374.332151 [doi]
AB  - 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 x 
      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 x 10(6) 
      cells/kg), medium (1 x 10(6) cells/kg) and high (4 x 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 the gamma-aminobutyric acid type A (GABA(A)) receptor expression by 
      the effective doses indicates that GABA(A) receptors are possible candidates for 
      therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, 
      this study revealed that intrathecal implantation of 1 x 10(6) hUC-MSCs/kg is an 
      alternative approach for treating subacute SCI.
FAU - Cao, Ting-Ting
AU  - Cao TT
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou, Guangdong Province, China.
FAU - Chen, Huan
AU  - Chen H
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou, Guangdong Province, China.
FAU - Pang, Mao
AU  - Pang M
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University; Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery; Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, Guangdong Province, 
      China.
FAU - Xu, Si-Si
AU  - Xu SS
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou, Guangdong Province, China.
FAU - Wen, Hui-Quan
AU  - Wen HQ
AD  - Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, 
      Guangzhou, Guangdong Province, China.
FAU - Liu, Bin
AU  - Liu B
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University; Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery; Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, Guangdong Province, 
      China.
FAU - Rong, Li-Min
AU  - Rong LM
AD  - Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen 
      University; Guangdong Provincial Center for Engineering and Technology Research 
      of Minimally Invasive Spine Surgery; Guangdong Provincial Center for Quality 
      Control of Minimally Invasive Spine Surgery, Guangzhou, Guangdong Province, 
      China.
FAU - Li, Mang-Mang
AU  - Li MM
AD  - Department of Cell Biology, School of Basic Medical Sciences, Southern Medical 
      University, Guangzhou, Guangdong Province, China.
LA  - eng
PT  - Journal Article
PL  - India
TA  - Neural Regen Res
JT  - Neural regeneration research
JID - 101316351
PMC - PMC8820722
OTO - NOTNLM
OT  - effective dose
OT  - human umbilical cord mesenchymal stem cells
OT  - intrathecal implantation
OT  - ion channels
OT  - neurotransmitter receptors
OT  - spinal cord injury
OT  - subacute spinal cord injury
OT  - gamma-aminobutyric acid type A (GABAA) receptors
COIS- None
EDAT- 2022/01/13 06:00
MHDA- 2022/01/13 06:01
PMCR- 2022/01/07
CRDT- 2022/01/12 06:13
PHST- 2022/01/12 06:13 [entrez]
PHST- 2022/01/13 06:00 [pubmed]
PHST- 2022/01/13 06:01 [medline]
PHST- 2022/01/07 00:00 [pmc-release]
AID - NeuralRegenRes_2022_17_8_1785_332151 [pii]
AID - NRR-17-1785 [pii]
AID - 10.4103/1673-5374.332151 [doi]
PST - ppublish
SO  - Neural Regen Res. 2022 Aug;17(8):1785-1794. doi: 10.4103/1673-5374.332151.