PMID- 36104746
OWN - NLM
STAT- MEDLINE
DCOM- 20220916
LR  - 20220922
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 13
IP  - 1
DP  - 2022 Sep 14
TI  - Effects of hypoxia-preconditioned HucMSCs on neovascularization and follicle 
      survival in frozen/thawed human ovarian cortex transplanted to immunodeficient 
      mice.
PG  - 474
LID - 10.1186/s13287-022-03167-6 [doi]
LID - 474
AB  - BACKGROUND: The massive loss of follicles in the early stage of ovarian tissue 
      transplantation is considered a significant restriction to the efficacy of 
      ovarian tissue cryopreservation (OTC) and transplantation (OT). The use of 
      mesenchymal stem cells (MSCs) before transplantation of ovarian fragments 
      shortened the hypoxic period and boosted neovascularization. 
      Hypoxia-preconditioned MSCs can enhance the potential of angiogenesis. Can 
      hypoxia-preconditioned human umbilical cord mesenchymal stem cell (HucMSCs) and 
      ovarian tissue co-xenotransplantation improve more neovascularization and 
      subsequently more follicle survival in human ovarian tissue? METHODS: 
      Frozen-thawed cortical pieces from 4 patients were transplanted into the 
      bilateral renal capsule of immune-deficient nude mice without HucMSCs or 
      normoxia/hypoxia-preconditioned HucMSCs. Sixty-four mice were randomly 
      distributed into 4 groups. In each group, the mice were euthanized for blood 
      and/or graft retrieval on post-transplantation days 3 (n = 8) and 7 (n = 8), 
      respectively. Non-grafted frozen-thawed ovarian fragment was taken for 
      non-grafted control. Grafts were histologically processed and analysed for 
      follicle density and atretic follicles by HE, neovascularization by CD34 and CD31 
      immunohistochemical staining, primordial follicle growth by Ki67 staining, and 
      apoptosis of stromal cell and follicles by immunofluorescence using TUNEL. The 
      ROS and TAC levels of grafted and non-grafted tissue were assessed. We evaluated 
      the protein expression of HIF1alpha, VEGFA, pAkt, Akt, and GDF9 in grafted and 
      non-grafted ovarian tissue. E2, Prog, AMH, and FSH levels in the plasma of mice 
      were measured after 3 and 7 days of OT. RESULTS: Hypoxia-preconditioned HucMSCs 
      positively protect the grafted ovarian tissue by significantly decreasing the 
      apoptosis and increasing higher expression of CD31, CD34, and VEGFA for earlier 
      angiogenesis. They are crucial to preserving the resting primordial follicle pool 
      by modulation of follicle death. CONCLUSION: This is the first study to 
      demonstrate that co-transplantation of hypoxia-preconditioned HucMSC with ovarian 
      tissue improved earlier vascularization of ovarian grafts in the early 
      post-grafting period, which correlates with increased follicle survival and 
      reduced apoptosis. The HIF1alpha/VEGFA signal pathways may play an important role in 
      elucidating the mechanisms of action of hypoxia-preconditioned HucMSCs with 
      regard to OT and clinical implementation.
CI  - (c) 2022. The Author(s).
FAU - Cheng, Jiaojiao
AU  - Cheng J
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Ruan, Xiangyan
AU  - Ruan X
AUID- ORCID: 0000-0001-7777-247X
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China. ruanxiangyan@ccmu.edu.cn.
AD  - Department for Women's Health, University Women's Hospital and Research Center 
      for Women's Health, University of Tuebingen, 72076, Tuebingen, Germany. 
      ruanxiangyan@ccmu.edu.cn.
FAU - Li, Yanglu
AU  - Li Y
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Du, Juan
AU  - Du J
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Jin, Fengyu
AU  - Jin F
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Gu, Muqing
AU  - Gu M
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Zhou, Qi
AU  - Zhou Q
AD  - Department of Gynecology, Beijing Obstetrics and Gynecology Hospital, Capital 
      Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, 
      100026, People's Republic of China.
FAU - Xu, Xin
AU  - Xu X
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Yang, Yu
AU  - Yang Y
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Wang, Husheng
AU  - Wang H
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
FAU - Mueck, Alfred Otto
AU  - Mueck AO
AD  - Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology 
      Hospital, Capital Medical University, Beijing Maternal and Child Health Care 
      Hospital, No. 251, Yaojiayuan Road, Chaoyang District, Beijing, 100026, People's 
      Republic of China.
AD  - Department for Women's Health, University Women's Hospital and Research Center 
      for Women's Health, University of Tuebingen, 72076, Tuebingen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220914
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Hypoxia
MH  - Mice
MH  - Mice, Nude
MH  - *Ovarian Follicle
MH  - *Ovary
MH  - Umbilical Cord
PMC - PMC9476266
OTO - NOTNLM
OT  - Endocrine restoration
OT  - Fertility preservation
OT  - Follicle survival
OT  - Human umbilical cord mesenchymal stem cell
OT  - Hypoxia
OT  - Hypoxia-inducible factor 1alpha
OT  - Neovascularization
OT  - Ovarian tissue transplantation
OT  - PI3K/protein kinase B signalling pathway
COIS- The authors declare that they have no competing interests.
EDAT- 2022/09/15 06:00
MHDA- 2022/09/17 06:00
PMCR- 2022/09/14
CRDT- 2022/09/14 23:45
PHST- 2022/05/10 00:00 [received]
PHST- 2022/08/26 00:00 [accepted]
PHST- 2022/09/14 23:45 [entrez]
PHST- 2022/09/15 06:00 [pubmed]
PHST- 2022/09/17 06:00 [medline]
PHST- 2022/09/14 00:00 [pmc-release]
AID - 10.1186/s13287-022-03167-6 [pii]
AID - 3167 [pii]
AID - 10.1186/s13287-022-03167-6 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2022 Sep 14;13(1):474. doi: 10.1186/s13287-022-03167-6.