Research Progress in Promotion of Tissue Regeneration and Reconstruction with Exosomes Derived from Mesenchymal Stem Cells

CHEN Man-yu, WANG Qi-guang, FAN Yu-jiang

Abstract

In regenerative medicine, stem cell therapy is an effective strategy for tissue regeneration and has a positive therapeutic effect on the regeneration and repair of defective tissues. In recent years, a series of studies have shown that the positive effects of stem cell therapy are mediated by exosomes released by the paracrine action of mesenchymal stem cells. Researchers have thus proposed a novel treatment strategy to use stem-cell-derived exosomes alone for tissue regeneration and repair, and affirmed through studies that the effects achieved were comparable to those of stem-cell-based therapies. Therefore, as a promising treatment strategy, exosome-based tissue regeneration treatment measures have been extensively studied. In this review, we discussed the latest knowledge of exosomes and the research progress in the regeneration and repair of related connective tissues, including the regeneration of bones, cartilage, skin, spinal cord and tendons, and briefly discussed the corresponding mechanisms. In addition, the challenges and prospects of tissue regeneration and repair based on mesenchymal stem cell exosomes were discussed.

 

Keywords: Mesenchymal stem cells, Exosomes, Tissue regeneration and repair

 

Full Text:

PDF


References


] WANG Y， CHEN X， CAO W， et al. Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications. Nat Immunol，2014，15(11): 1009–1016.

PENG X， XU H， ZHOU Y， et al. Human umbilical cord mesenchymal stem cells attenuate cisplatin-induced acute and chronic renal injury. Exp Biol Med，2013，238(8): 960–970.

MURATA D， AKIEDA S， MISUMI K， et al. Osteochondral regeneration with a scaffold-free three-dimensional construct of adipose tissue-derived mesenchymal stromal cells in pigs. Tissue Eng Regen Med， 2017，15(1): 101–113.

SROUJI S， BEN-DAVID D， FROMIGUE O， et al. Lentiviral-mediated integrin alpha 5 expression in human adult mesenchymal stromal cells promotes bone repair in mouse cranial and long-bone defects. Hum Gene Ther，2012，23(2): 167–172.

INGAVLE G C， GIONET-GONZALES M， VORWALD C E， et al. Injectable mineralized microsphere-loaded composite hydrogels for bone repair in a sheep bone defect model. Biomaterials，2019，197: 119–128.

GYOENGYOESI M， WOJAKOWSKI W， LEMARCHAND P， et al. Meta-analysis of cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data. Circ Res， 2015，116(8): 1346–1360.

SWAMINATHAN M， STAFFORD-SMITH M， CHERTOW G M， et al. Allogeneic mesenchymal stem cells for treatment of AKI after cardiac surgery. J Am Soc Nephrol，2018，29(1): 260–267.

KIM N， CHO S G. New strategies for overcoming limitations of mesenchymal stem cell-based immune modulation. Int J Stem Cells， 2015，8(1): 54–68.

GNECCHI M， HE H M， LIANG O D， et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med，2005，11(4): 367–368.

LENER T， GIMONA M， AIGNER L， et al. Applying extracellular vesicles based therapeutics in clinical trials—An ISEV position paper. J Extracell Vesicles，2015，4: 30087[2021-04-18]. https://doi.org/10. 3402/jev.v4.30087.

MATEESCU B， KOWAL E J K， VAN BALKOM B W M， et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA—An ISEV position paper. J Extracell Vesicles，2017，6: 1286095[2021-04-18]. https://doi.org/10.1080/20013078.2017.1286095.

HUNTER D J， BIERMA-ZEINSTRA S. Osteoarthritis. The Lancet，2019， 393(9991): 1745–1759.

WITWER K W， VAN BALKOM B W M， BRUNO S， et al. Defining mesenchymal stromal cell (MSC)-derived small extracellular vesicles for therapeutic applications. J Extracell Vesicles，2019，8: 1609206[2021-04-18]. https://doi.org/10.1080/20013078.2019.1609206.

CHEN P， ZHENG L， WANG Y， et al. Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration. Theranostics， 2019，9(9): 2439–2459.

CHEN Y， XUE K， ZHANG X， et al. Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells. Stem Cell Res Ther，2018，9: 318[2021-04-18]. https://doi.org/10.1186/s13287-018-1047-2.

COSENZA S， RUIZ M， TOUPET K， et al. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep，2017，7: 16214[2021-04-18]. https://doi.org/10.1038/s41598-017-15376-8.

LIU X， YANG Y， LI Y， et al. Integration of stem cell-derived exosomes with in situ hydrogel glue as a promising tissue patch for articular cartilage regeneration. Nanoscale，2017，9(13): 4430–4438.

LIU Y， ZOU R， WANG Z， et al. Exosomal KLF3-AS1 from hMSCs promoted cartilage repair and chondrocyte proliferation in osteoarthritis. Biochem J，2018，475(22): 3629–3638.

MAO G， ZHANG Z， HU S， et al. Exosomes derived from miR-92a-3p-overexpressing human mesenchymal stem cells enhance chondrogenesis and suppress cartilage degradation via targeting WNT5A. Stem Cell Res Ther，2018，9: 247[2021-04-18]. https://doi.org/10.1186/s13287-018-1004-0.

TAO S C， YUAN T， ZHANG Y L， et al. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics，2017，7(1): 180–195.

ZHANG S， CHUAH S J， LAI R C， et al. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials，2018，156: 16–27.

ZHU Y， WANG Y， ZHAO B， et al. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther，2017，8(1): 64[2021-04-18]. https://doi. org/10.1186/s13287-017-0510-9.

TOFINO-VIAN M， ISABEL GUILLEN M， PEREZ DEL CAZ M D， et al. Extracellular vesicles from adipose-derived mesenchymal stem cells downregulate senescence features in osteoarthritic osteoblasts. Oxid Med Cell Longev，2017，2017: 7197598[2021-04-18]. https://doi.org/10. 1155/2017/7197598.

VONK L A， VAN DOOREMALEN S F J， LIV N， et al. Mesenchymal stromal/stem cell-derived extracellular vesicles promote human cartilage regeneration in vitro. Theranostics，2018，8(4): 906–920.

WU J， KUANG L， CHEN C， et al. miR-100-5p-abundant exosomes derived from infrapatellar fat pad MSCs protect articular cartilage and ameliorate gait abnormalities via inhibition of mTOR in osteoarthritis. Biomaterials，2019，206: 87–100.

ZHANG S P， TEO K Y W， CHUAH S J， et al. MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials，2019，200: 35–47.

OTSURU S， DESBOURDES L， GUESS A J， et al. Extracellular vesicles released from mesenchymal stromal cells stimulate bone growth in osteogenesis imperfecta. Cytotherapy，2018，20(1): 62–73.

CHEW J R J， CHUAH S J， TEO K Y W， et al. Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomater，2019，89: 252–264.

ZHANG Y， HAO Z， WANG P， et al. Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1 alpha-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif，2019，52(2): e12570[2021-04-18]. https://doi.org/10. 1111/cpr.12570.


Refbacks

  • There are currently no refbacks.