Cartilage Regeneration in Humans with Adipose Tissue-Derived Stem Cells and Adipose Stromal Vascular Fraction Cells: Updated Status

Pak, Jaewoo; Lee, Jung Hun; Pak, Natalie Jieun; Pak, Yoon K.; Park, Kwang Seung; Jeon, Jeong Ho; Jeong, Byeong Chul; Lee, Sangeun

doi:10.3390/ijms19072146

Cited by 79 publications

(71 citation statements)

References 104 publications

(162 reference statements)

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“…Adipose-tissue-derived cells are successfully applied for the reconstruction and regeneration of damaged or diseased tissues where common therapies fail (Pak et al, 2018). Their high regenerative potential is underlined by several clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction

Nürnberger¹,

Lindner²,

Maier³

et al. 2019

eCM

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The prerequisite for a successful clinical use of autologous adipose-tissue-derived cells is the highest possible regenerative potential of the applied cell population, the stromal vascular fraction (SVF). Current isolation methods depend on high enzyme concentration, lysis buffer, long incubation steps and mechanical stress, resulting in single cell dissociation. The aim of the study was to limit cell manipulation and obtain a derivative comprising therapeutic cells (microtissue-SVF) without dissociation from their natural extracellular matrix, by employing a gentle good manufacturing practice (GMP)-grade isolation. The microtissue-SVF yielded larger numbers of viable cells as compared to the improved standard-SVF, both with low enzyme concentration and minimal dead cell content. It comprised stromal tissue compounds (collagen, glycosaminoglycans, fibroblasts), capillaries and vessel structures (CD31 + , smooth muscle actin + ). A broad range of cell types was identified by surface-marker characterisation, including mesenchymal, haematopoietic, pericytic, blood and lymphatic vascular and epithelial cells. Subpopulations such as supra-adventitial adipose-derived stromal/stem cells and endothelial progenitor cells were significantly more abundant in the microtissue-SVF, corroborated by significantly higher potency for angiogenic tube-like structure formation in vitro. The microtissue-SVF showed the characteristic phenotype and tri-lineage mesenchymal differentiation potential in vitro and an immunomodulatory and pro-angiogenic secretome. In vivo implantation of the microtissue-SVF combined with fat demonstrated successful graft integration in nude mice. The present study demonstrated a fast and gentle isolation by minor manipulation of liposuction material, achieving a therapeutically relevant cell population with high vascularisation potential and immunomodulatory properties still embedded in a fraction of its original matrix.

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Section: Introductionmentioning

confidence: 99%

Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction

Nürnberger¹,

Lindner²,

Maier³

et al. 2019

eCM

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“…have been reported to be involved in communication among cells and shown to participate in a wide spectrum of cellular processes, including the pathological development and progression of arthritis (5,6). in the present study, secreted exosomes were isolated from adScs and incubated with activated SFs obtained from an obese patient with oa.…”

Section: Adsc-derived Exosomes (Adsc-exos) Decrease Inflammation In Amentioning

confidence: 86%

“…exosomes have been shown to participate in stem cell-or progenitor cell-mediated tissue regeneration. in the bones, exosomes regulate multiple signaling processes involved in the differentiation of osteocytes and bone architecture maintenance in a paracrine manner (6). For instance, exosomes were detected in the bone microenvironment, where they modulated intracellular or intercellular signaling, by targeting the same cells, adjacent cells or distant organs (16).…”

Section: Discussionmentioning

confidence: 99%

“…a previous study suggested that the age of the donor does not have a significant role in the phenotype or function of adScs (4). Most clinical trials which utilize adScs for oa treatment have been based on the autologous cells from the stromal vascular fraction, as have most of the in vivo studies (6,7). although the use of adScs for treating oa has been gaining attention clinically and experimentally, the underlying mechanisms by which adScs attenuate oa have not been fully elucidated.…”

mentioning

confidence: 99%

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Exosomes from adipose‑derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR‑145 and miR‑221

Zhao

Chen²,

Peng³

et al. 2020

Mol Med Report

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osteoarthritis (oa) is one of the most prevalent joint disorders globally. Patients suffering from oa are often obese and adiposity is linked to chronic inflammation. In the present study, the potential of using exosomes isolated from adipose-derived stem cells (adScs) as a therapeutic tool for reducing chronic inflammation and promoting chondrogenesis was investigated using patient-derived primary cells. First, it was tested whether patient-derived adScs could differentiate into chondrogenic and osteogenic lineages. The adScs were then used as a source of exosomes. it was found that exosomes isolated from adScs, when co-cultured with activated synovial fibroblasts, downregulated the expression of pro-inflammatory markers interleukin (il)-6, nF-κB and tumor necrosis factor-α, while they upregulated the expression of the anti-inflammatory cytokine IL-10; without exosomes, the opposite observations were made. in addition, inflammation-inflicted oxidative stress was induced in vitro by stimulating chondrocytes with H 2 o 2 . Treatment with exosomes protected articular chondrocytes from H 2 o 2 -induced apoptosis. Furthermore, exosome treatment promoted chondrogenesis in periosteal cells and increased chondrogenic markers, including collagen type ii and β-catenin; inhibition of Wnt/β-catenin, using the antagonist icG-001, prevented exosome-induced chondrogenesis. Periosteal cells treated with exosomes exhibited higher levels of microrna (mir)-145 and mir-221. The upregulation of mir-145 and mir-221 was associated with the enhanced proliferation of periosteal cells and chondrogenic potential, respectively. The present study provided evidence in support for the use of patient-derived exosomes, produced from adScs, for potential chondrogenic regeneration and subsequent amelioration of osteoarthritis.

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“…(1) their capability of homing/migration, incorporation and further differentiation within the host, and (2) a battery of morphogens, chemokines and factors secreted by the MSC (Pak et al, 2018). This second characteristic is being currently harnessed to treat essentially knee and hip joints in osteoarthritis by intra-articular injection (Desando et al, 2013;Zhang et al, 2016;Cosenza et al, 2017;Seong et al, 2017).…”

Section: Joint Repairmentioning

confidence: 99%

Adipose-derived mesenchymal stem/stromal cells: from the lab bench to the basic concepts for clinical translation

Frontini-López¹,

Gojanovich²,

Masone³

et al. 2018

Biocell

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In the last years, much work has shown that the most effective repair system of the body is represented by stem cells, which are defined as undifferentiated precursors that own unlimited or prolonged self-renewal ability, which also have the potential to transform themselves into various cell types through differentiation.All tissues that form the body contain many different types of somatic cells, along with stem cells that are called 'mesenchymal stem (or stromal) cells' (MSC). In certain circumstances, some of these MSC migrate to injured tissues to replace dead cells or to undergo differentiation to repair it.The discovery of MSC has been an important step in regenerative medicine because of their high versatility. Moreover, the finding of a method to isolate MSC from adipose tissue, so called 'adipose-derived mesenchymal stem cells' (ASC), which share similar differentiation capabilities and isolation yield that is greater than other MSC, and less bioethical concerns compared to embryonic stem cells, have created self-praised publicity to procure almost any treatment with them. Here, we review the current techniques for isolation, culture and differentiation of human ASC (hASC), and describe them in detail. We also compile some advantages of the hASC over other stem cells, and provide some concepts that could help finding strategies to promote their therapeutic efficiency. BIOCELLISSN 1667-5746 (on-line) 2018 42 (3): [67][68][69][70][71][72][73][74][75][76][77]

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Cartilage Regeneration in Humans with Adipose Tissue-Derived Stem Cells and Adipose Stromal Vascular Fraction Cells: Updated Status

Cited by 79 publications

References 104 publications

Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction

Adipose-tissue-derived therapeutic cells in their natural environment as an autologous cell therapy strategy: the microtissue-stromal vascular fraction

Exosomes from adipose‑derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR‑145 and miR‑221

Adipose-derived mesenchymal stem/stromal cells: from the lab bench to the basic concepts for clinical translation

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