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Regenerative Medicine for Polycystic Ovary Syndrome: Stem Cell-Based Therapies and Brown Adipose Tissue Activation

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Abstract

Polycystic ovary syndrome (PCOS) is a pathological condition prevalent among women of reproductive age: it is associated with varied etiological factors (lifestyle, genetic, environmental…) and characterized by an increased polycystic morphology of the ovaries leading to disturbances in the menstrual cycle and its correlated infertility. Interconnections between PCOS, obesity, and insulin resistance have been recently investigated thoroughly in the scientific community; these findings directed PCOS therapies into unraveling possibilities to target insulin resistance and central adiposity as efficient treatment. On the other hand, brown adipose tissue is known to possess a thermogenic activity that increases lipolysis and directly attenuates fat deposition. Therefore, brown adipose tissue activation lands itself as a potential target for reducing obesity and its induced insulin resistance, subsequently rescuing PCOS phenotypes. In addition, regenerative medicine has proven efficacy in resolving PCOS-associated infertility and its metabolic symptoms. In particular, many stem/progenitor cells have been verified to possess the differentiation capacity into functional brown adipocytes. Thus, throughout this review, we will discuss the different brown adipose tissue activation strategies and stem-cell-based therapies applied to PCOS models and the possible combination of both therapeutic approaches to synergistically act on the activation of brown adipose tissue and attenuate PCOS-correlated infertility and retract the consequences of the metabolic syndrome on the physiological state of patients.

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Data Availability

The data used to support the findings of this review are available from the corresponding author upon request.

Code Availability

Not applicable.

Abbreviations

ACTH :

Adrenocorticotropic hormone

ADSC :

Adipose-derived mesenchymal stem cells

BAT :

Brown adipose tissue

BM-MSC :

Bone marrow-derived mesenchymal stem cells

CVD :

Cardiovascular disease

CYP :

Cytochrome P

DHEA :

Dehydroepiandrosterone

FAH :

Functional adrenal hyperandrogenism

FSH :

Follicle stimulating hormone

GnRH :

Gonadotropin-releasing hormone

iPSC :

Induced-pluripotent stem cells

LH :

Luteinizing hormone

MSC :

Mesenchymal stem cells

PCOM :

Polycystic ovary morphology

PCOS :

Polycystic ovary syndrome

PET :

Positron emission tomography

TC :

Thecal cells

TSC :

Thecal stem cells

UCP-1 :

Uncoupling protein-1

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Acknowledgements

We would like to thanks Edde Associtation – Lebanon for their support to LIT Laboratory. We would like to thank Dr Rim Nassar for the technical support she gave concerning the Biorender logiciel. Also, we would like to thank the Lebanese University for all the support. The English grammar and spelling of this manuscript have been professionally edited by Mrs Ferial Srour, we would like to thank her for proofreading the manuscript.

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Authors and Affiliations

  1. Laboratoire d’Innovation Thérapeutique, “Stem Cell, Organogenesis and Regenerative Medicine” Master Program, Faculty of Sciences, Lebanese University, Beirut, Lebanon

    Mario Karam

  2. Department of Pediatrics, Faculty of Medicine, Lebanese University, Hadat, Lebanon

    Hélène Najjar

  3. Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon

    Marwan El Sabban

  4. Laboratoire d’Innovation Thérapeutique, Departments of Biology, Chemistry and Biochemistry, Faculty of Sciences II, Lebanese University, Fanar, Lebanon

    Aline Hamade & Fadia Najjar

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Fadia Najjar and Aline Hamade had the idea for the article. All the authors performed the literature search and data analysis. The first draft of the manuscript was written by Mario Karam. Hélène Najjar, Marwan El Sabban, Aline Hamade and Fadia Najjar critically revised the manuscript for intellectual content. All the authors read and approved the final manuscript.

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Correspondence to Marwan El Sabban, Aline Hamade or Fadia Najjar.

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Karam, M., Najjar, H., El Sabban, M. et al. Regenerative Medicine for Polycystic Ovary Syndrome: Stem Cell-Based Therapies and Brown Adipose Tissue Activation. Stem Cell Rev and Rep 19, 853–865 (2023). https://doi.org/10.1007/s12015-023-10505-5

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