Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration

Shukla, Lipi; Yuan, Yinan; Shayan, Ramin; Greening, David W.; Karnezis, Tara

doi:10.3389/fphar.2020.00158

Cited by 132 publications

(109 citation statements)

References 257 publications

(398 reference statements)

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“…ADSCs are defined as mesenchymal cells within adipose tissue with multipotent differentiation and self-renewal capacity ( 23 ). Since the initial discovery of ADSCs, their molecular profiles has been the subject of debate.…”

Section: Discussionmentioning

confidence: 99%

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors

Nie

Zhang

et al. 2020

Mol Med Rep

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Dedifferentiated adipose cells (DAs) and adipose-derived stem cells (ADSCs) are two of the primary types of stem cells derived from adipose tissue, which have been reported to possess similar characteristics, but also exhibit unique phenotypic and functional advantages. However, several reports have described inconsistent results regarding their differences in multilineage differentiation function. Moreover, to the best of our knowledge, there are no studies assessing their myogenic ability, or the differences in the transcriptome between the two cell types derived from lipoaspirates via tumescent liposuction from the same donors. The aim of the present study was to compare the properties and expression profiles of these cell types. Subcutaneous adipose tissue of three female patients (aged 23–30 years) with a physiological BMI (19.1–23.9 kg/m 2 ) were obtained during tumescent liposuction of the abdomen or the thigh. The stromal vascular fraction and mature adipocytes were obtained via collagenase digestion, and ADSCs and DAs were cultured successively. To determine the differences between DAs and ADSCs after 6–7 passages, cell proliferation assays, phenotypic assessment, differentiation assays and high-throughput RNA sequencing (seq) were used. Similar cell morphologies, proliferation dynamics, surface markers and transcriptome expression profiles were observed between the DAs and ADSCs. Whilst there were notable individual differences in the osteogenic, lipogenic, chondrogenic and myogenic abilities of the DAs and ADSCs, it was difficult to determine their differentiation potential based only on the cell source. Interestingly, the myogenic ability was relatively stronger in cells with relatively weaker lipogenic ability. Only 186 differentially expressed genes between the two groups were identified using RNAseq. Several of these genes were involved in biological functions such as transcription regulation, protein translation regulation, cytokine interactions and energy metabolism regulation. The results of the present study suggested a similar functional potential of DAs and ADSCs from young donors undergoing tumescent liposuction operation in regeneration areas and the balance of the differentiative ability of the same cell populations. These data may provide a foundation for further clinical administration of stem cells derived from adipose tissues in therapy.

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Section: Discussionmentioning

confidence: 99%

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors

Nie

Zhang

et al. 2020

Mol Med Rep

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“…Thirteen severe cases of COVID-19 patients under invasive mechanical ventilation have received doses of allogenic ADSCs and presented improved clinical and biological outcomes [ 29 ]. Used at autologous and allogenic state, these cells have gained interest [ 13 , 14 , 19 , 23 , 27 , 169 ] provided that MSCs and derivatives are performed in GMP conditions and regulated by the FDA or EMA.…”

Section: Refining New Cell-based Therapies In the Context Of Covid-19mentioning

confidence: 99%

Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19

2021

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Adipose-derived stem cells (ADSCs) have raised big interest in therapeutic applications in regenerative medicine and appear to fulfill the criteria for a successful cell therapy. Their low immunogenicity and their ability to self-renew, to differentiate into different tissue-specific progenitors, to migrate into damaged sites, and to act through autocrine and paracrine pathways have been altogether testified as the main mechanisms whereby cell repair and regeneration occur. The absence of standardization protocols in cell management within laboratories or facilities added to the new technologies improved at patient’s bedside and the discrepancies in cell outcomes and engraftment increase the limitations on their widespread use by balancing their real benefit versus the patient safety and security. Also, comparisons across pooled patients are particularly difficult in the fact that multiple medical devices are used and there is absence of harmonized assessment assays despite meeting regulations agencies and efficient GMP protocols. Moreover, the emergence of the COVID-19 breakdown added to the complexity of implementing standardization. Cell- and tissue-based therapies are completely dependent on the biological manifestations and parameters associated to and induced by this virus where the scope is still unknown. The initial flow chart identified for stem cell therapies should be reformulated and updated to overcome patient infection and avoid significant variability, thus enabling more patient safety and therapeutic efficiency. The aim of this work is to highlight the major guidelines and differences in ADSC processing meeting the current good manufacturing practices (cGMP) and the cellular therapy-related policies. Specific insights on standardization of ADSCs proceeding at different check points are also presented as a setup for the cord blood and bone marrow.

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“…ADSCs can secrete a variety of extracellular vesicles (EVs), exosomes, and soluble factors [ 43 ]. An extensive range of chemokines, cytokines, growth factors, mRNAs, and micro-RNAs are released by ADSCs that participate in angiogenesis, lymphangiogenesis, immune modulation, and reducing fibrogenesis [ 22 , 43 ]. These anti-apoptotic factors and pro-angiogenic factors can affect activities of the nervous system, immune system, heart, muscles, and even ordinary somatic cells through endocrine and paracrine methods and have been demonstrated to play a therapeutic role in bone reconstruction, nerve protection, heart regeneration, and soft tissue regeneration [ 43 – 47 ].…”

Section: Basic Functions Of Adscsmentioning

confidence: 99%

“…Thus, surgeons mixed an additional percentage of isolated and in vitro cultured ADSCs into lipoaspirate to obtain a novel fat graft, which was called cell-assisted lipotransfer (CAL) [ 21 ]. Both preclinical and clinical studies suggested that ADSC-based CAL could improve the survival of fat grafts and has been well used especially in breast augmentation and facial lipoatrophy [ 22 ]. Nevertheless, due to the complication and economic limitations of isolation and expansion procedures of ADSCs, surgeons prefer to applying stromal vascular fraction (SVF) instead to deliver fresh ADSCs for CAL in clinical trials rather than ADSCs.…”

Section: Introductionmentioning

confidence: 99%

Adipose tissue-derived stem cells in breast reconstruction: a brief review on biology and translation

et al. 2021

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Recent developments in adipose-derived stromal/stem cell (ADSC) biology provide new hopes for tissue engineering and regeneration medicine. Due to their pluripotent activity, paracrine activity, and immunomodulatory function, ADSCs have been widely administrated and exhibited significant therapeutic effects in the treatment for autoimmune disorders, neurodegenerative diseases, and ischemic conditions both in animals and human clinical trials. Cell-assisted lipotransfer (CAL) based on ADSCs has emerged as a promising cell therapy technology and significantly improved the fat graft retention. Initially applied for cosmetic breast and facial enhancement, CAL has found a potential use for breast reconstruction in breast cancer patients. However, more challenges emerge related to CAL including lack of a standardized surgical procedure, the controversy in the effectiveness of CAL, and the potential oncogenic risk of ADSCs in cancer patients. In this review, we summarized the latest research and intended to give an outline involving the biological characteristics of ADSCs as well as the preclinical and clinical application of ADSCs.

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Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration

Cited by 132 publications

References 257 publications

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors

Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19

Adipose tissue-derived stem cells in breast reconstruction: a brief review on biology and translation

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Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration

Cited by 132 publications

References 257 publications

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and&nbsp;adipose‑derived stem cells from young donors

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and&nbsp;adipose‑derived stem cells from young donors

Overview of current adipose-derived stem cell (ADSCs) processing involved in therapeutic advancements: flow chart and regulation updates before and after COVID-19

Adipose tissue-derived stem cells in breast reconstruction: a brief review on biology and translation

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Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors

Differentiation potential and mRNA profiles of human dedifferentiated adipose cells and adipose‑derived stem cells from young donors