Regenerative Effect of Vaginal Injections of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in Ovariectomized Rats

Ya-Wei Lai^{1

2

3}, Sheng-Hua Wu^{4

5

6}, Ping-Ruey Chou^{7

8}, Yu-Chi Wang¹, Jwu-Lai Yeh⁹, Tsai-Ming Lin¹⁰, Chee-Yin Chai¹¹, Cheng-Hsien Tsai¹², Shu-Hung Huang^{13

14

15}

Affiliations

¹ Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
² Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, 820, Taiwan.
³ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁴ Department of Anesthesiology, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, 820, Taiwan.
⁵ Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
⁶ Department of Anesthesiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁷ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁸ Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
⁹ Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
¹⁰ Charming Institute of Aesthetic and Regenerative Surgery (CIARS), 2F.-1, No. 172, Ziqiang 2nd Road, Qianjin District, Kaohsiung, 801, Taiwan.
¹¹ Departments of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
¹² BIONET Therapeutics Corp., 1F, No.28, Ln. 36, Xinhu 1st Rd., Neihu Dist., Taipei City, 114, Taiwan.
¹³ Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. huangsh63@gmail.com.
¹⁴ Professor of Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung, 807, Taiwan. huangsh63@gmail.com.
¹⁵ Division of Plastic Surgery, Department of Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, 812, Taiwan. huangsh63@gmail.com.

PMID: 41275445
DOI: 10.1007/s00266-025-05444-0

Regenerative Effect of Vaginal Injections of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in Ovariectomized Rats

Ya-Wei Lai et al. Aesthetic Plast Surg. 2025.

. 2025 Nov 23.

doi: 10.1007/s00266-025-05444-0. Online ahead of print.

Authors

Ya-Wei Lai^{1

2

3}, Sheng-Hua Wu^{4

5

6}, Ping-Ruey Chou^{7

8}, Yu-Chi Wang¹, Jwu-Lai Yeh⁹, Tsai-Ming Lin¹⁰, Chee-Yin Chai¹¹, Cheng-Hsien Tsai¹², Shu-Hung Huang^{13

14

15}

Affiliations

¹ Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
² Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, 820, Taiwan.
³ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁴ Department of Anesthesiology, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, 820, Taiwan.
⁵ Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
⁶ Department of Anesthesiology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁷ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
⁸ Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan.
⁹ Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
¹⁰ Charming Institute of Aesthetic and Regenerative Surgery (CIARS), 2F.-1, No. 172, Ziqiang 2nd Road, Qianjin District, Kaohsiung, 801, Taiwan.
¹¹ Departments of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
¹² BIONET Therapeutics Corp., 1F, No.28, Ln. 36, Xinhu 1st Rd., Neihu Dist., Taipei City, 114, Taiwan.
¹³ Division of Plastic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, 807, Taiwan. huangsh63@gmail.com.
¹⁴ Professor of Department of Surgery, School of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung, 807, Taiwan. huangsh63@gmail.com.
¹⁵ Division of Plastic Surgery, Department of Surgery, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, 812, Taiwan. huangsh63@gmail.com.

PMID: 41275445
DOI: 10.1007/s00266-025-05444-0

Abstract

Background: In genitourinary syndrome of menopause (GSM), reduced estrogen levels cause several pathological changes in the vaginal mucosa, including epithelial thinning, decreased blood flow and glycogen production, loss of elasticity, and mucus production. Umbilical cord mesenchymal stem cell-derived exosomes (ucMSC-ex) facilitate intercellular communication and play a key role in mucosal regeneration and immune response modulation.

Objectives: We examined the therapeutic effect of ucMSC-ex injection on vaginal atrophy in ovariectomized rats.

Methods: Tangential flow filtration was used to extract ucMSC-ex. Female Sprague-Dawley rats were divided into three groups: a group receiving sham treatment, a group receiving sham treatment after ovariectomy, and a group receiving vaginal ucMSC-ex injection after ovariectomy. Treatment efficacy was determined by analyzing rat vaginal tissue to observe changes in the vaginal epithelium and in collagenesis, angiogenesis, estrogen receptor count, vaginal lubrication, and inflammatory response.

Results: Our preliminary histological results indicated that ucMSC-ex injection enhanced structural restoration, collagen formation, angiogenesis, estrogen receptor expression, vaginal lubrication, cellular proliferation, and anti-inflammatory response in vaginal tissue, indicating its regenerative potential as a treatment for GSM.

Conclusions: Our findings support the therapeutic potential of exosome therapy in alleviating the symptoms of GSM by promoting tissue regeneration and vascularization, restoring vaginal lubrication, and reducing inflammation.

No level assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Keywords: Genitourinary syndrome of menopause (GSM); Umbilical cord mesenchymal stem cell–derived exosomes (ucMSC-ex); Vaginal lubrication; Vaginal rejuvenation.

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Conflict of interest statement

Declarations. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. Human and Animal Rights: This article does not contain any studies with human participants. Our animal protocols were approved by the Institutional Animal Care and Use Committee of Kaohsiung Medical University (IACUC 112047). Informed Consent: For this type of study, informed consent is not required.

References

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1. DiBonaventura M, et al. The association between vulvovaginal atrophy symptoms and quality of life among postmenopausal women in the United States and Western Europe. J Womens Health (Larchmt). 2015;24(9):713–22. - PubMed - DOI
1. Coleman SR. Long-term survival of fat transplants: controlled demonstrations. Aesthet Plast Surg. 2020;44(4):1268–72. - DOI

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Regenerative Effect of Vaginal Injections of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in Ovariectomized Rats

Affiliations

Regenerative Effect of Vaginal Injections of Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes in Ovariectomized Rats

Authors

Affiliations

Abstract

Conflict of interest statement

References

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