Cartilage Repair by Mesenchymal Stem Cell-Derived Exosomes: Preclinical and Clinical Trial Update and Perspectives

Taghiyar, Leila; Jahangir, Shahrbano; Ravari, Mojtaba Khozaei; Shamekhi, Mohammad Amin; Eslaminejad, Mohamadreza Baghaban

doi:10.1007/5584_2021_625

Cited by 17 publications

(12 citation statements)

References 147 publications

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“…When transplanted in vivo into specific organs, ADSCs demonstrate a high regenerative potential and impart to specific cell formation and to the repletion of the blood vessels probably due to their intrinsic multipotency [ 31 , 32 ]. Mesenchymal cells of human adult tissue can be directed toward an organ-specific cell phenotype when in contact with differentiating primary organ progenitor cells in vitro and in vivo [ 32 , 33 , 34 ], whereas ADSCs are likely unable to produce new muscle fibers de novo or even to promote a complete skeletal muscle program [ 35 , 36 ]. In this context, ADSC-based therapy may contribute to the further development of tissue engineering to recover tissue defects or damage after oncologic surgery leading to cosmetic problems [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Organ-Specific Differentiation of Human Adipose-Derived Stem Cells in Various Organs of Xenotransplanted Rats: A Pilot Study

Park

Choi

Kang

et al. 2022

Life

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Adipose-derived stem cells (ADSCs) are potential therapeutics considering their self-renewal capacity and ability to differentiate into all somatic cell types in vitro. The ideal ADSC-based therapy is a direct injection into the relevant organs. The objective of this study was to investigate the viability and safety of intra-organ human ADSC (h-ADSC) xenotransplants in vivo. Subcutaneous adipose tissue from the abdominal area of 10 patients was sampled. h-ADSCs were isolated from adipose tissue samples and identified using immunofluorescence antibodies. Multi-differentiation potential assays for adipocytes, osteocytes, and chondrocytes were performed. Cultured h-ADSCs at passage 4 were transplanted into multiple organs of 17 rats, including the skin, subcutaneous layer, liver, kidney, pancreas, and spleen. The h-ADSC-injected organs excised after 100 days were examined, and the survival of h-ADSCs was measured by quantitative real-time polymerase chain reaction (qRT-PCR) using specific human and rat target genes. h-ADSCs confirmed by stem cell phenotyping were induced to differentiate into adipogenic, osteogenic, and chondrogenic lineages in vitro. All rats were healthy and exhibited no side effects during the study; the transplanted h-ADSCs did not cause inflammation and were indiscernible from the native organ cells. The presence of transplanted h-ADSCs was confirmed using qRT-PCR. However, the engrafted survival rates varied as follows: subcutaneous fat (70.6%), followed by the liver (52.9%), pancreas (50.0%), kidney (29.4%), skin (29.4%), and spleen (12.5%). h-ADSCs were successfully transplanted into a rat model, with different survival rates depending on the organ.

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Section: Discussionmentioning

confidence: 99%

Organ-Specific Differentiation of Human Adipose-Derived Stem Cells in Various Organs of Xenotransplanted Rats: A Pilot Study

Park

Choi

Kang

et al. 2022

Life

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“…EV transfer of miRNA has been extensively researched during the past decade. In particular, MSCs isolated from diverse sources (bone marrow, synovial membrane, adipose tissue, umbilical cord and embryonic cells) were reported to be able to transduce miRNA effects through secretion of EVs [37][38][39], mainly through leading to immunomodulation. Here, we demonstrated that chondrocytes also secrete miRNA through EVs and that the content of the EVs can be controlled by the expression of the miRNA.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles Allow Epigenetic Mechanotransduction between Chondrocytes and Osteoblasts

Shang

Böker

Taheri

et al. 2021

IJMS

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MicroRNAs (miRNAs) can be transported in extracellular vesicles (EVs) and are qualified as possible messengers for cell–cell communication. In the context of osteoarthritis (OA), miR-221-3p has been shown to have a mechanosensitive and a paracrine function inside cartilage. However, the question remains if EVs with miR-221-3p can act as molecular mechanotransducers between cells of different tissues. Here, we studied the effect of EV-mediated transport in the communication between chondrocytes and osteoblasts in vitro in a rat model. In silico analysis (Targetscan, miRWalk, miRDB) revealed putative targets of miRNA-221-3p (CDKN1B/p27, TIMP-3, Tcf7l2/TCF4, ARNT). Indeed, transfection of miRNA-221-3p in chondrocytes and osteoblasts resulted in regulation of these targets. Coculture experiments of transfected chondrocytes with untransfected osteoblasts not only showed regulation of these target genes in osteoblasts but also inhibition of their bone formation capacity. Direct treatment with chondrocyte-derived EVs validated that chondrocyte-produced extracellular miR-221-3p was responsible for this effect. Altogether, our study provides a novel perspective on a possible communication pathway of a mechanically induced epigenetic signal through EVs. This may be important for processes at the interface of bone and cartilage, such as OA development, physiologic joint homeostasis, growth or fracture healing, as well as for other tissue interfaces with differing biomechanical properties.

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“…As a cell-free therapeutic method, many studies have reported the protective or destructive role of EVs by affecting cartilage repair, 39 synovialis, 40 and subchondral bone remodeling 41 in the progress of OA and raised considerable interests in the scientific research field. Although most cells could secret EVs, most studies preferred to utilize different mesenchymal stem cells (MSCs) as the source of EVs due to the particular function such as differentiation, regeneration, and anti-inflammation of MSCs in the treatment of OA.…”

Section: The Application Of Evs-mirnas In Oa Treatmentmentioning

confidence: 99%

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective

Shang¹,

Yan²,

Yang³

et al. 2022

JIR

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Osteoarthritis (OA) is a whole joint disease characterized by synovitis, cartilage destruction, and subchondral bone sclerosis and cyst. Despite decades’ study, effective treatment is rare for this chronic disease. Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptosis bodies, are nano-sized vesicles with a cargo containing biologically active agents, such as nucleic acids, lipids, and proteins. As a group of short non-coding RNAs, microRNAs (miRNAs) can be delivered by parental cells secreted EVs. Negatively regulate the target mRNAs at the posttranscriptional level and regulate gene expression in recipient cells without modifying gene sequence. Recently, most studies focused on the function of EVs mediated miRNAs in the pathophysiological process of OA. However, all kinds of EVs specific and OA specific factors might influence the administration of EVs-miRNAs, especially the precise quantitative management. As a result, the flourishing of current research about EVs in the laboratory might not promote the relevant clinical transformation in OA treatment. In this review, we reviewed the present application of EVs-miRNAs in the therapeutic of OA and further analyzed the potential factors that might influence its application. Further progress in the quantitative management of EVs-miRNAs would accelerate the clinical transformation of miRNAs enriched EVs in the OA field.

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Cartilage Repair by Mesenchymal Stem Cell-Derived Exosomes: Preclinical and Clinical Trial Update and Perspectives

Cited by 17 publications

References 147 publications

Organ-Specific Differentiation of Human Adipose-Derived Stem Cells in Various Organs of Xenotransplanted Rats: A Pilot Study

Organ-Specific Differentiation of Human Adipose-Derived Stem Cells in Various Organs of Xenotransplanted Rats: A Pilot Study

Extracellular Vesicles Allow Epigenetic Mechanotransduction between Chondrocytes and Osteoblasts

The Application of Extracellular Vesicles Mediated miRNAs in Osteoarthritis: Current Knowledge and Perspective

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