Application of cattle placental stem cells for treating ovarian follicular cyst

doi:10.4252/wjsc.v12.i11.1366

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World Journal of Stem Cells

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World J Stem Cells. Nov 26, 2020; 12(11): 1366-1376
Published online Nov 26, 2020. doi: 10.4252/wjsc.v12.i11.1366

Application of cattle placental stem cells for treating ovarian follicular cyst

Shao-Yu Peng, Tsung-Hsin Wu, Tzu-Yi Lin, Ling-Yien Hii, Kok-Seong Chan, Tzu-Yen Fu, Shen-Chang Chang, Perng-Chih Shen, Kang-You Liu, Steven W. Shaw

Shao-Yu Peng, Tsung-Hsin Wu, Tzu-Yen Fu, Perng-Chih Shen, Kang-You Liu, Department of Animal Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan

Tzu-Yi Lin, Steven W. Shaw, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan

Ling-Yien Hii, Kok-Seong Chan, Steven W. Shaw, Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 105, Taiwan

Shen-Chang Chang, Kaohsiung Animal Propagation Station, Livestock Research Institute, Council of Agriculture, Executive Yuan, Pingtung 912, Taiwan

Steven W. Shaw, Prenatal Cell and Gene Therapy Group, Institute for Women's Health, University College London, London WC1E 6HU, United Kingdom

Author contributions: Peng SY and Shaw SW designed and coordinated the study; Peng SY, Wu TH, and Fu TY performed the experiments; Chang SC and Shen PC analyzed the data; Peng SY, Liu KY, and Shaw SW interpreted the data; Peng SY drafted the manuscript; Lin TY, Hii LY, and Chan KS revised the manuscript; Shaw SW critically reviewed the manuscript; All authors were involved in the amendment and approval of the final manuscript.

Supported by Chang Gung Memorial Hospital, No. CPRPG1J0021; Ministry of Science and Technology Taiwan, No. MOST 108-2314-B-182A-085, No. MOST 105-2313-B-020 -001 -MY2, and No. MOST 108-2313-B-020 -007 -MY3.

Institutional animal care and use committee statement: All procedures involving animals conformed to the internationally accepted principle for care and use of animals from the National Pingtung University of Science and Technology Affidavit of Approval of Animal Use Committee (IACUC protocol number: NPUST-104-048).

Conflict-of-interest statement: There are no conflicts of interest regarding the publication of this paper.

Data sharing statement: No additional data are available.

ARRIVE guidelines statement: The authors had read the ARRIVE guidelines. The manuscript was prepared and revised according to the ARRIVE guidelines.

Corresponding author: Steven W. Shaw, MD, PhD, Associate Professor, Director, Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, No. 199 Dunhua North Road, Taipei 105, Taiwan. dr.shaw@me.com

Received: March 12, 2020
Peer-review started: March 12, 2020
First decision: May 26, 2020
Revised: July 2, 2020
Accepted: September 8, 2020
Article in press: September 8, 2020
Published online: November 26, 2020
Processing time: 259 Days and 6.4 Hours

ARTICLE HIGHLIGHTS

Research background

High humidity and temperature in Taiwan have significant effects on the reproductivity of Holstein cattle, which results in the occurrence of bovine ovarian follicular cyst (OFC). Because of economic loss from OFC, manual rupture and hormone injection have been advocated. However, these incomplete treatments decrease the conception rate and increase hormone resistance in cattle. In recent years, stem cells have been extensively utilized to repair or replace damaged tissues. Injection of stem cells might become an effective modality to treat OFC.

Research motivation

Through angiogenesis promotion and immune modulation, mesenchymal stem cells (MSCs) showed the potential in the treatment of several diseases. Besides, MSCs can be non-invasively collected from the placenta without much ethical concern. With a great source of stem cells, transplantation treatment could be conducted practically.

Research objectives

This study established the possibility of using cattle placental stem cells (CPSCs) as a treatment modality for OFC in cows.

Research methods

The cattle with OFC were divided into three groups: control (BC1 and BC2), hormone (H1 and H2), and CPSC (PS1 and PS2) treatment groups. In the hormone treatment group, the cows were given gonadotrophin-releasing hormone (GnRH)-prostaglandin-GnRH injection with or without drainage of follicular fluid. In the CPSC treatment groups, CPSCs were isolated from the placenta. The cows were given ovarian injection of 1 × 10⁶ or 6 × 10⁶ CPSCs with drainage. Then OFC was scanned by ultrasound once a week for a total of seven times. The concentrations of estradiol and progesterone in serum were tested in the same period. The estrus cycle was analyzed by food intake and activity. If estrus was detected, artificial insemination was conducted. The cow was monitored by ultrasound for confirmation of pregnancy.

Research results

After 7 d of culture, CPSCs were successfully isolated from placental pieces. CPSCs proliferated significantly every 24 h and highly expressed MSC markers, such as CD44. In an ultrasound study, more subsided OFCs were observed with drainage of follicular fluid. The recovery rates were 0%, 50%, 50%, 75%, 75%, and 75% in BC1, BC2, H1, H2, PS1, and PS2, respectively. The estrus rate was 0%, 100%, 25%, 75%, 75%, and 75% in BC1, BC2, H1, H2, PS1, and PS2, respectively. Two fetuses were born in H2 and PS1.

Research conclusions

Cows with CPSC injection achieved higher recovery, estrus, and inseminated conception rates. This approach shows efficacy in treating cows with OFC.

Research perspectives

CPSC injection could serve as an alternative treatment for OFC. In the future, other reproductive disorders might also be investigated with stem cell therapy.