Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT)

There is an increasing concern that the term adipose tissue-derived stem cell (ASC) is inappropriately used to refer to the adipose stromal vascular fraction (SVF). To evaluate the accuracy and quality of reporting, 116 manuscripts on the application of ASC in humans and animals were examined based on the 2013 published International Federation for Adipose Therapeutics and Science (IFATS)/ International Society for Cellular Therapy (ISCT) joint statement and in reference to current guidelines for clinical trials and preclinical studies. It is disconcerting that 4 among the 47 papers or 8.51% (CI 2.37–20.38) surveyed after publication of IFATS/ISCT statement reported using ASCs but in fact they used unexpanded cells. 28/47 or 59.57% (CI 44.27–73.63) explicitly reported that adherent cells were used, 35/47 or 74.47% (CI 59.65–86.06) identified expression of surface markers, and 25/47 or 53.19% (CI 14.72–30.65) verified the multilineage potential of the cells. While there are a number of papers examined in this survey that were not able to provide adequate information on the characteristics of ASCs used with some erroneously referring to the SVF as stem cells, there are more room for improvement in the quality of reporting in the application of ASCs in humans and animals.

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Adipose-Derived Stem Cells for Future Regenerative System Medicine

The Indonesian Biomedical Journal ◽

10.18585/inabj.v4i2.164 ◽

2012 ◽

Vol 4 (2) ◽

pp. 59

Author(s):

Yani Lina ◽

Andi Wijaya

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Adipose Tissue ◽

Regenerative Medicine ◽

Adult Stem Cells ◽

Stromal Vascular Fraction ◽

Human Adipose Tissue ◽

Lytic Enzymes ◽

Stromal Stem Cells

BACKGROUND: The potential use of stem cell-based therapies for repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of disease. Despite the advances, the availability of stem cells remaining a challenge for both scientist and clinicians in pursuing regenerative medicine. CONTENT: Subcutaneous human adipose tissue is an abundant and accessible cell source for applications in tissue engineering and regenerative medicine. Routinely, the adipose issue is digested with collagenase or related lytic enzymes to release a heterogeneous population for stromal vascular fraction (SVF) cells. The SVF cells can be used directly or can be cultured in plastic ware for selection and expansion of an adherent population known as adipose-derived stromal/stem cells (ASCs). Their potential in the ability to differentiate into adipogenic, osteogenic, chondrogenic and other mesenchymal lineages, as well in their other clinically useful properties, includes stimulation of angiogenesis and suppression of inflammation.SUMMARY: Adipose tissue is now recognized as an accessible, abundant and reliable site for the isolation of adult stem cels suitable for the application of tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models.KEYWORDS: adipose tissue, adult stem cells, regenerative medicine, mesenchymal stem cells

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Adipose-derived stem cells in the treatment of knee osteoarthritis: from extraction methods to the preparation of the transplant

Research Society and Development ◽

10.33448/rsd-v11i1.24669 ◽

2022 ◽

Vol 11 (1) ◽

pp. e24111124699

Author(s):

Laynna de Carvalho Schweich-Adami ◽

Larissa Corrêa Hermeto ◽

Silvana Marques Caramalac ◽

Andréia Conceição Milan Brochado Antoniolli-Silva ◽

Rodrigo Juliano Oliveira

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Knee Osteoarthritis ◽

Cellular Therapy ◽

Extraction Methods ◽

International Federation ◽

Adipose Derived Stem Cells ◽

Real Presence ◽

Number Of Cells

Introduction: Recent studies have investigated the use of adipose tissue as source of mesenchymal stem cells in the treatment of knee osteoarthritis in humans. However, there are still several protocols being performed. Objective: Analyze the protocols published in the literature in the last ten years and to investigate how they are being carried out and if they are following the criteria adopted by the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Methodology: Articles from the PubMed, ScienceDirect and Lilacs database published in January / 2010 until the present time, which were evaluated in order to investigate the use of adipose-derived stem cells in the treatment of knee osteoarthritis. Results: Thirty four articles were evaluated in its entiraty. The abdominal area was the most choosen to do the liposuction, however the quantities of adipose tissue removed and the number of cells transplanted was variable. It is hightlited the enzimatic digestion of adipose tissue with collagenase as extraction method. Only 14 articles complied all the 3 criteria required to prove the real presence of mesenchymal stem cells in the samples that was transplanted. However, all the articles showed improvement of function and pain. Final considerations: Thus, even the results found are promising, the evidence is still limited in humans and the variability of the methodology makes it difficult to standardize the technique, also its implementation as a reference in the treatment of knee osteoarthritis.

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Processing and Ex Vivo Expansion of Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells for the Development of an Advanced Therapy Medicinal Product for Use in Humans

Cells ◽

10.3390/cells10081908 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1908

Author(s):

Anna Labedz-Maslowska ◽

Agnieszka Szkaradek ◽

Tomasz Mierzwinski ◽

Zbigniew Madeja ◽

Ewa Zuba-Surma

Keyword(s):

Adipose Tissue ◽

Medicinal Product ◽

Stromal Cells ◽

Manufacturing Process ◽

Cellular Therapy ◽

Ex Vivo ◽

Ex Vivo Expansion ◽

Advanced Therapy Medicinal Product ◽

Differentiation Potential ◽

Advanced Therapy

Adipose tissue (AT) represents a commonly used source of mesenchymal stem/stromal cells (MSCs) whose proregenerative potential has been widely investigated in multiple clinical trials worldwide. However, the standardization of the manufacturing process of MSC-based cell therapy medicinal products in compliance with the requirements of the local authorities is obligatory and will allow us to obtain the necessary permits for product administration according to its intended use. Within the research phase (RD), we optimized the protocols used for the processing and ex vivo expansion of AT-derived MSCs (AT-MSCs) for the development of an Advanced Therapy Medicinal Product (ATMP) for use in humans. Critical process parameters (including, e.g., the concentration of enzyme used for AT digestion, cell culture conditions) were identified and examined to ensure the high quality of the final product containing AT-MSCs. We confirmed the identity of isolated AT-MSCs as MSCs and their trilineage differentiation potential according to the International Society for Cellular Therapy (ISCT) recommendations. Based on the conducted experiments, in-process quality control (QC) parameters and acceptance criteria were defined for the manufacturing of hospital exemption ATMP (HE-ATMP). Finally, we conducted a validation of the manufacturing process in a GMP facility. In the current study, we presented a process approach leading to the optimization of processing and the ex vivo expansion of AT-MSCs for the development of ATMP for use in humans.

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Derivation, characterization, and in vitro cell regeneration of canine white adipose tissue-derived mesenchymal stem cells obtained from a mesenteric region

The Journal of Basic and Applied Zoology ◽

10.1186/s41936-021-00222-1 ◽

2021 ◽

Vol 82 (1) ◽

Author(s):

Anirban Mandal ◽

Ajeet Kumar Jha ◽

Dew Biswas ◽

Shyamal Kanti Guha

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

White Adipose Tissue ◽

Stromal Vascular Fraction ◽

Cell Regeneration ◽

Wound Healing Assay ◽

Chain Reaction ◽

Polymerase Chain

Abstract Background The study was conducted to assess the characterization, differentiation, and in vitro cell regeneration potential of canine mesenteric white adipose tissue-derived mesenchymal stem cells (AD-MSCs). The tissue was harvested through surgical incision and digested with collagenase to obtain a stromal vascular fraction. Mesenchymal stem cells isolated from the stromal vascular fraction were characterized through flow cytometry and reverse transcription-polymerase chain reaction. Assessment of cell viability, in vitro cell regeneration, and cell senescence were carried out through MTT assay, wound healing assay, and β-galactosidase assay, respectively. To ascertain the trilineage differentiation potential, MSCs were stained with alizarin red for osteocytes, alcian blue for chondrocytes, and oil o red for adipocytes. In addition, differentiated cells were characterized through a reverse transcription-polymerase chain reaction. Results We observed the elongated, spindle-shaped, and fibroblast-like appearance of cells after 72 h of initial culture. Flow cytometry results showed positive expression for CD44, CD90, and negative expression for CD45 surface markers. Population doubling time was found 18–24 h for up to the fourth passage and 30±0.5 h for the fifth passage. A wound-healing assay was used to determine cell migration rate which was found 136.9 ± 4.7 μm/h. We observed long-term in vitro cell proliferation resulted in MSC senescence. Furthermore, we also found that the isolated cells were capable of differentiating into osteogenic, chondrogenic, and adipogenic lineages. Conclusions Mesenteric white adipose tissue was found to be a potential source for isolation, characterization, and differentiation of MSCs. This study might be helpful for resolving the problems regarding the paucity of information concerning the basic biology of stem cells. The large-scale use of AD-MSCs might be a remedial measure in regenerative medicine.

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Eine aktuelle Übersicht über die Einflussfaktoren der Stammzellspender auf das regenerative Potential von Fettgewebsstammzellen

Handchirurgie · Mikrochirurgie · Plastische Chirurgie ◽

10.1055/a-1250-7878 ◽

2020 ◽

Vol 52 (06) ◽

pp. 521-532

Author(s):

Constanze Kuhlmann ◽

Thilo Ludwig Schenck ◽

Elisabeth Maria Haas ◽

Riccardo Giunta ◽

Paul Severin Wiggenhauser

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Stromal Vascular Fraction ◽

National Library ◽

Regenerative Therapie

Zusammenfassung Hintergrund Nicht nur regenerative Therapie wie zellassistierter Lipotransfer (cell assisted lipotransfer) sondern auch präklinische experimentelle Studien verwenden in der Plastischen Chirurgie Stammzellen aus Fettgewebe, sogenannte Adipose tissue-derived Stem Cells (ASCs). Hierbei haben allerdings vom jeweiligen Stammzellspender abhängige Faktoren einen entscheidenden Einfluss auf die Zellausbeute und das regenerative Potential von ASCs und der Stromal vascular Fraction (SVF). Ziel dieser Übersichtsarbeit war es daher, diese Einflussfaktoren des Stammzellspenders darzustellen und anhand des aktuellen Wissenstands zu beurteilen. Methoden Es erfolgte eine intensive Literaturrecherche in der der National Library of Medicine, mit Fokus auf Einflussfaktoren der Stammzellspender, die eine Beeinflussung der Zellausbeute und des regenerativen Potentials von humanen ASCs und SVF in vorherigen Studien gezeigt haben. Ergebnisse Aktuell gibt es eine Vielzahl von Studien, welche sich mit den Einflussfaktoren des Stammzellspenders auseinandersetzen. Allerdings sind diese Faktoren sehr inhomogen und teilweise sogar widersprüchlich, so dass hier noch weiterer Forschungsbedarf besteht. Dennoch gibt es einige Faktoren, die gemäß der aktuellen Literatur gehäuft untersucht wurden: Alter, Geschlecht, Gewicht, Nebenerkrankungen (z. B. Diabetes, Lipödem) sowie spezielle Medikamente (Antidepressiva, Antihormontherapie) und Chemotherapie. Schlussfolgerung Wir empfehlen, bei experimentellen und klinischen Arbeiten mit ASCs/SVF eine Charakterisierung des Patientenkollektivs zu veröffentlichen, so dass mögliche Beeinflussungen durch oben genannte Faktoren kommuniziert werden und eine bessere Vergleichbarkeit von Studien ermöglicht wird. Darüber hinaus kann aber auch mit einer präzisen Anamnese und körperlichen Untersuchung vorab ein möglichst homogenes Patientenkollektiv für die Sammlung von Proben für wissenschaftliche Arbeiten konstruiert werden. Auch könnten die Ergebnisse dazu beitragen, den Erfolg zukünftiger ASC-basierter Therapien einzuschätzen.

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Characterization of the stromal vascular fraction and of the adipose-derived mesenchymal stromal cells isolated from the two compartments of the subcutaneous abdominal adipose tissue in human

Cytotherapy ◽

10.1016/s1465324921003534 ◽

2021 ◽

Vol 23 (5) ◽

pp. S60

Author(s):

J. Laloze ◽

B. Chaput ◽

A. Prevost ◽

L. Casteilla ◽

A. Desmouliere ◽

...

Keyword(s):

Adipose Tissue ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Stromal Vascular Fraction ◽

Abdominal Adipose Tissue ◽

Subcutaneous Abdominal Adipose Tissue

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Adipose Derived-Mesenchymal Stem Cells Viability and Differentiating Features for Orthopaedic Reparative Applications: Banking of Adipose Tissue

Stem Cells International ◽

10.1155/2016/4968724 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 18

Author(s):

Ilaria Roato ◽

Daniela Alotto ◽

Dimas Carolina Belisario ◽

Stefania Casarin ◽

Mara Fumagalli ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Articular Cartilage ◽

Tissue Banking ◽

Stromal Vascular Fraction ◽

Single Infusion ◽

Knee Arthritis ◽

Symptomatic Knee

Osteoarthritis is characterized by loss of articular cartilage also due to reduced chondrogenic activity of mesenchymal stem cells (MSCs) from patients. Adipose tissue is an attractive source of MSCs (ATD-MSCs), representing an effective tool for reparative medicine, particularly for treatment of osteoarthritis, due to their chondrogenic and osteogenic differentiation capability. The treatment of symptomatic knee arthritis with ATD-MSCs proved effective with a single infusion, but multiple infusions could be also more efficacious. Here we studied some crucial aspects of adipose tissue banking procedures, evaluating ATD-MSCs viability, and differentiation capability after cryopreservation, to guarantee the quality of the tissue for multiple infusions. We reported that the presence of local anesthetic during lipoaspiration negatively affects cell viability of cryopreserved adipose tissue and cell growth of ATD-MSCs in culture. We observed that DMSO guarantees a faster growth of ATD-MSCs in culture than trehalose. At last, ATD-MSCs derived from fresh and cryopreserved samples at −80°C and −196°C showed viability and differentiation ability comparable to fresh samples. These data indicate that cryopreservation of adipose tissue at −80°C and −196°C is equivalent and preserves the content of ATD-MSCs in Stromal Vascular Fraction (SVF), guaranteeing the differentiation ability of ATD-MSCs.

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Efficient differentiation of beige adipocytes from adult human adipose-derived stem/stromal cells

10.21203/rs.3.pex-888/v1 ◽

2020 ◽

Author(s):

Amar M. Singh ◽

Liang Zhang ◽

John Avery ◽

Stephen Dalton

Keyword(s):

Stem Cells ◽

Cell Therapy ◽

Drug Screening ◽

Stromal Cells ◽

High Efficiency ◽

Disease Modelling ◽

Serum Free ◽

Beige Adipocytes ◽

Free Media ◽

Stromal Stem Cells

Abstract Beige adipocytes (also known as brite adipocytes) have significant utility for numerous applications, such as drug screening, cell therapy, and disease modelling. However, a high-efficiency protocol from human adult adipose-derived stem/stromal stem cells (ADSC) has not been described. The protocol described here achieves beige adipocyte purities of >92% in a fully-defined, serum-free media cocktail, which enables these downstream applications. This method provides a significant leap forward over previously described, serum-based protocols that were inconsistent and inefficient.

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