PMID- 36726973
OWN - NLM
STAT- MEDLINE
DCOM- 20230203
LR  - 20230217
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Pre-clinical efficacy evaluation of human umbilical cord mesenchymal stem cells 
      for ischemic stroke.
PG  - 1095469
LID - 10.3389/fimmu.2022.1095469 [doi]
LID - 1095469
AB  - OBJECTIVE: This study explored the underlying therapeutic mechanism of human 
      umbilical cord mesenchymal stem cells (hUCMSCs) for ischemic stroke (IS), and 
      determined the optimal administration time windows and dose-effect relationship. 
      METHODS: The levels of SDF-1alpha, IL-10, IL-6, TNF-alpha, BDNF, IL-1beta, and VEGF-A 
      factors in serum and brain tissue lysate were measured by ELISA. The pathological 
      status of brain tissues was evaluated by Hematoxylin-Eosin (HE) staining, and 
      apoptosis of nerve cells was detected by tunel. The protein expression of CXCR-4, 
      NeuN, and Nestin in the brain tissues was assessed through immunofluorescence. 
      The balance beam, forelimb muscle strength, and limb placement were tested on 
      MCAO rats at different time points and doses. The infarct area of the rat brain 
      tissues was measured at the end of the experiment. RESULTS: The hUCMSC treatment 
      during the acute phase of MCAO significantly reduced the secretion of IL-6, 
      TNF-alpha, IL-1beta but increased IL-10 in serum, and the levels of SDF-alpha and BDNF in 
      serum and brain tissues lysate were also increased. The pathological results 
      showed that there were more neurons in the treatment group compared to the model 
      group. Immunofluorescence assays showed that the expression of CXCR4、Nestin、NeuN 
      was relatively higher than that in the model group. The d4 and d7 treatment 
      significantly improves the motor function, promotes the recovery of forelimb 
      muscle strength, increases the forelimb placement rate and reduces the scope of 
      cerebral infarction, but the d14 treatment group has less therapeutic effect 
      compared to the d4 and d7 treatment. The 2x10(7)/kg treatment showed the best 
      therapeutic effect, followed by the 1x10(7)/kg treatment, and the worst is 
      0.5x10(7)/kg treatment from the test of balance beam, forelimb muscle strength, 
      limb placement and the infarct area of the rat brain tissues. CONCLUSION: The 
      hUCMSCs can inhibit the infiltration of inflammatory cells in the brain tissue, 
      and promote the repair of brain tissue structure and function. Early intervention 
      by injecting high-dose of hUCMSCs can significantly improve the recovery of 
      neurological/motor function and reduce the size of cerebral infarction in rats.
CI  - Copyright (c) 2023 Shen, Wang, Zhu, Jiang, Xie, Zhang, Lv, Liu, Wang, Qi and Wang.
FAU - Shen, Danpeng
AU  - Shen D
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Wang, Hongwei
AU  - Wang H
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Zhu, Hongyan
AU  - Zhu H
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Jiang, Cuibao
AU  - Jiang C
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Xie, Fan
AU  - Xie F
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Zhang, Hongpeng
AU  - Zhang H
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Lv, Qian
AU  - Lv Q
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Liu, Qi
AU  - Liu Q
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Wang, Zhiqiang
AU  - Wang Z
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Qi, Nianmin
AU  - Qi N
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Research and Experimental Development Department, Asia Stem Cell Regenerative 
      Pharmaceutical Co. Ltd, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20230113
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 130068-27-8 (Interleukin-10)
RN  - 0 (Nestin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Interleukin-6)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - Interleukin-10/metabolism
MH  - *Ischemic Stroke/metabolism
MH  - Nestin/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Interleukin-6/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cerebral Infarction
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Umbilical Cord
MH  - Treatment Outcome
PMC - PMC9885855
OTO - NOTNLM
OT  - Dose-effect relationship
OT  - Ischemic stroke
OT  - MCAO
OT  - Time windows
OT  - hUCMSCs
COIS- All authors were employed by company Asia Stem Cell Regenerative Pharmaceutical 
      Co. Ltd.
EDAT- 2023/02/03 06:00
MHDA- 2023/02/04 06:00
PMCR- 2022/01/01
CRDT- 2023/02/02 02:05
PHST- 2022/11/11 00:00 [received]
PHST- 2022/12/29 00:00 [accepted]
PHST- 2023/02/02 02:05 [entrez]
PHST- 2023/02/03 06:00 [pubmed]
PHST- 2023/02/04 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1095469 [doi]
PST - epublish
SO  - Front Immunol. 2023 Jan 13;13:1095469. doi: 10.3389/fimmu.2022.1095469. 
      eCollection 2022.