PMID- 35690871
OWN - NLM
STAT- MEDLINE
DCOM- 20220614
LR  - 20220729
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Jun 11
TI  - Preclinical study of human umbilical cord mesenchymal stem cell sheets for the 
      recovery of ischemic heart tissue.
PG  - 252
LID - 10.1186/s13287-022-02919-8 [doi]
LID - 252
AB  - BACKGROUND: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been 
      widely used due to their multipotency, a broad range of sources, painless 
      collection, and compliance with standard amplification. Cell sheet technology is 
      a tissue engineering methodology requiring scaffolds free, and it provides an 
      effective method for cell transplantation. To improve the therapeutic efficacy, 
      we combined hUC-MSCs with cell sheet technology to evaluate the safety and 
      efficacy of hUC-MSC sheets in preclinical studies using appropriate animal 
      models. METHODS: hUC-MSC sheets were fabricated by hUC-MSCs from a cell bank 
      established by a standard operation process and quality control. Cytokine 
      secretion, immunoregulation, and angiopoiesis were evaluated in vitro. 
      Oncogenicity and cell diffusion assays of hUC-MSC sheets were conducted to verify 
      the safety of hUC-MSCs sheet transplantation in mice. To provide more meaningful 
      animal experimental data for clinical trials, porcine myocardial infarction (MI) 
      models were established by constriction of the left circumflex, and hUC-MSC 
      sheets were transplanted onto the ischemic area of the heart tissue. Cardiac 
      function was evaluated and compared between the experimental and MI groups. 
      RESULTS: The in vitro results showed that hUC-MSC sheets could secrete multiple 
      cellular factors, including VEGF, HGF, IL-6, and IL-8. Peripheral blood 
      mononuclear cells had a lower proliferation rate and lower TNF-alpha secretion when 
      co-cultured with hUC-MSC sheets. TH1 cells had a smaller proportion after 
      activation. In vivo safety results showed that the hUC-MSCs sheet had no 
      oncogenicity and was mainly distributed on the surface of the ischemic myocardial 
      tissue. Echocardiography showed that hUC-MSC sheets effectively improved the left 
      ventricular ejection fraction (LVEF), and the LVEF significantly changed 
      (42.25 +/- 1.23% vs. 66.9 +/- 1.10%) in the hUC-MSC transplantation group compared 
      with the MI group (42.52 +/- 0.65% vs. 39.55 +/- 1.97%) at 9 weeks. The infarct ratio 
      of the hUC-MSCs sheet transplantation groups was also significantly reduced 
      (14.2 +/- 4.53% vs. 4.00 +/- 2.00%) compared with that of the MI group. CONCLUSION: 
      Allogeneic source and cell bank established by the standard operation process and 
      quality control make hUC-MSCs sheet possible to treat MI by off-the-shelf drug 
      with universal quality instead of individualized medical technology.
CI  - (c) 2022. The Author(s).
FAU - Gao, Shuang
AU  - Gao S
AD  - BOE Regenerative Medicine Technology Co., Ltd., No. 9 JiuXianQiao North Road, 
      Beijing, 100015, China.
FAU - Jin, Yongqiang
AU  - Jin Y
AD  - Heart Center, First Hospital of Tsinghua University, No. 6 JiuXianQiao 1st Road, 
      Beijing, 10016, China.
FAU - Ma, Jianlin
AU  - Ma J
AD  - BOE Regenerative Medicine Technology Co., Ltd., No. 9 JiuXianQiao North Road, 
      Beijing, 100015, China.
FAU - Wang, Juan
AU  - Wang J
AD  - BOE Regenerative Medicine Technology Co., Ltd., No. 9 JiuXianQiao North Road, 
      Beijing, 100015, China.
FAU - Wang, Jing
AU  - Wang J
AD  - BOE Regenerative Medicine Technology Co., Ltd., No. 9 JiuXianQiao North Road, 
      Beijing, 100015, China.
FAU - Shao, Zehua
AU  - Shao Z
AD  - Heart Center of Henan Provincial People's Hospital, Zhengzhou University People's 
      Hospital, No. 7 Weiwu Road, Zhengzhou, 450003, China.
FAU - Fan, Taibing
AU  - Fan T
AD  - Children Heart Center, Fuwai Central China Cardiovascular Hospital, No. 1 Fuwai 
      Road, Zhengzhou, 450018, China.
FAU - Zhang, Mingkui
AU  - Zhang M
AD  - Heart Center, First Hospital of Tsinghua University, No. 6 JiuXianQiao 1st Road, 
      Beijing, 10016, China.
FAU - Chang, Dehua
AU  - Chang D
AUID- ORCID: 0000-0003-1546-6906
AD  - Department of Cell Therapy in Regenerative Medicine, The University of Tokyo 
      Hospital, 7-3-1 Honggo, Bunkyo-ku, Tokyo, 113-8655, Japan. 
      jot.sur@mail.u-tokyo.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220611
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
SB  - IM
MH  - Animals
MH  - Humans
MH  - Ischemia/metabolism
MH  - Leukocytes, Mononuclear
MH  - *Mesenchymal Stem Cell Transplantation/methods
MH  - *Mesenchymal Stem Cells/metabolism
MH  - Mice
MH  - *Myocardial Infarction/metabolism/therapy
MH  - Stroke Volume
MH  - Swine
MH  - Umbilical Cord
MH  - Ventricular Function, Left
PMC - PMC9188245
OTO - NOTNLM
OT  - Cell sheet
OT  - Ischemic myocardial tissue
OT  - Myocardial infarction
OT  - Safety of cell sheet
OT  - Umbilical cord mesenchymal stem cells
COIS- The authors declare that they have no competing interests.
EDAT- 2022/06/12 06:00
MHDA- 2022/06/15 06:00
PMCR- 2022/06/11
CRDT- 2022/06/11 23:41
PHST- 2022/03/29 00:00 [received]
PHST- 2022/05/03 00:00 [accepted]
PHST- 2022/06/11 23:41 [entrez]
PHST- 2022/06/12 06:00 [pubmed]
PHST- 2022/06/15 06:00 [medline]
PHST- 2022/06/11 00:00 [pmc-release]
AID - 10.1186/s13287-022-02919-8 [pii]
AID - 2919 [pii]
AID - 10.1186/s13287-022-02919-8 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2022 Jun 11;13(1):252. doi: 10.1186/s13287-022-02919-8.