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Exosomes derived from mesenchymal stromal cells: a promising treatment for pelvic floor dysfunction

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Abstract

Pelvic floor dysfunction (PFDs), which include pelvic organ prolapse (POP), stress urinary incontinence (SUI) and anal incontinence (AI), are common degenerative diseases in women that have dramatic effects on quality of life. The pathology of PFDs is based on impaired pelvic connective tissue supportive strength due to an imbalance in extracellular matrix (ECM) metabolism, the loss of a variety of cell types, such as fibroblasts, muscle cells, peripheral nerve cells, and oxidative stress and inflammation in the pelvic environment. Fortunately, exosomes, which are one of the major secretions of mesenchymal stromal cells (MSCs), are involved in intercellular communication and the modulation of molecular activities in recipient cells via their contents, which are bioactive proteins and genetic factors such as mRNAs and miRNAs. These components modify fibroblast activation and secretion, facilitate ECM modelling, and promote cell proliferation to enhance pelvic tissue regeneration. In this review, we focus on the molecular mechanisms and future directions of exosomes derived from MSCs that are of great value in the treatment of PFD.

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Abbreviations

PFD:

Pelvic floor disorders

POP:

Pelvic organ prolapse

SUI:

Stress urinary incontinence

AI:

Anal incontinence

ECM:

Extracellular matrix

MSC:

Mesenchymal stromal cell

AI:

Anal incontinence

PFMT:

Pelvic floor muscle physiotherapy

BF:

Biofeedback

FBR:

Foreign body response

FDA:

Food and drug administration

EMA:

European medicines agency

HIF-1α:

Hypoxia-inducible factor 1α

AGEs:

Advanced glycation end products

MMPs:

Matrix metalloproteinases

TIMPs:

Tissue inhibitors of matrix metalloproteinases

OS:

Oxidative stress

MnSOD:

Mitochondrial superoxide dismutase

GPX:

Glutathione peroxidase

EVs:

Extracellular vesicles

TEM:

Transmission electron microscopy

NTA:

Nanoparticle tracking analysis

HSP70:

Heat shock protein 70

TSG101:

Tumour-susceptibility gene 101

MVBs:

Multivesicular bodies

SNAREs:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors

ESCRT:

The endosomal sorting complex required for transport

MSCs-Ex:

Mesenchymal stromal cell-derived exosomes

HUCMSCs:

Human umbilical cord mesenchymal stromal cells

LPP:

Leak point pressure

eMSCs:

Human endometrial mesenchymal stromal cells

BMSCs:

Bone marrow mesenchymal stromal cells

ADSC:

Adipose-derived stromal cell

USC:

Urine-derived stromal cell (USC)

SCs:

Satellite cell

ERK:

Extracellular-regulated protein kinases

SIRT1:

Silent mating type information regulation 2 homologue 1 (SIRT1)

DRG:

Dorsal root ganglion

SMC:

Smooth muscle cell

AIF:

Apoptosis-inducing factor

PARP-1:

Upregulating poly ADP-ribose polymerase 1

PAR:

Poly ADP-ribose

JAG1:

Jagged1

ROS:

Reactive oxygen species

Nrf2:

Nuclear factor-E2-related factor 2

TLR4:

Toll-like receptor 4

dECM:

Decellularized scaffold ECM

TFF:

Tangential flow filtration

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Acknowledgements

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Funding

This work was supported by the Science and Technolog Commission of Shanghai Municipality (No.21Y11906700 to Yising Chen). Science Commission of Shangha and Technology Municipality (No.20Y11907300 to Yisong Chen).

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Authors and Affiliations

  1. Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 128 ShenYang Road, Shanghai, 200011, People’s Republic of China

    Leimei Xu, Yizhen Sima, Chengzhen Xiao & Yisong Chen

  2. Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai, China

    Leimei Xu, Yizhen Sima & Yisong Chen

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  1. Leimei Xu
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  2. Yizhen Sima
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  3. Chengzhen Xiao
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  4. Yisong Chen
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LMX drafted the manuscript; CZX contributed to the analysis of the results; and YZSM and YSC reviewed and modified the manuscript. All authors agreed on the final version. All authors read and approved the final manuscript.

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Correspondence to Yisong Chen.

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Xu, L., Sima, Y., Xiao, C. et al. Exosomes derived from mesenchymal stromal cells: a promising treatment for pelvic floor dysfunction. Human Cell 36, 937–949 (2023). https://doi.org/10.1007/s13577-023-00887-6

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