Breaking down fat: ISCT and IFATS position statement on stromal cells from the adipose tissue

by Alexey Bersenev on April 9, 2013 · 0 comments

in adipose

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We’re starting a new series – “Breaking Down Fat“. In this series we will talk about identification, characterization and clinical processing of potentially therapeutic cell populations from adipose tissue. We are starting this series in response to the growing trend of wide (mostly uncontrolled) clinical use adipose-derived cells and some controversies/ misconceptions in the field. There are many ongoing debates on proper characterization, clinical use and regulation adipose tissue-derived cells. We would like to invite you to contribute to this series, share your knowledge and make it valuable for community!

I’d like to start from ISCT and IFATS official position statement on fresh and cultured stromal cells from the human adipose tissue. This statement was just published online Yesterday. International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT) are two professional organizations with authority and expertise, which could and should take a lead on creating such statements/ recommendations in order to navigate and clarify controversial issues for stakeholders:

The goal of this paper is to provide initial guidance to academia, industry and regulatory authorities regarding the minimal properties expected for adipose tissue-derived cells.

This document does not intend to establish policies that may restrict future advances; rather, it is designed to provide guidance that promotes further biologic clarifications, best clinical practices and safety to improve efficacious adipose tissue-derived cell therapies that benefit society.

The statement gives recommendations for basic characterization of freshly isolated stromal vascular fraction (SVF) and cultured adipose tissue-derived stromal cells (ASCs). These two cell types, derived from fat, frequently referred in mass media and medical literature as “adipose stem cells“. However, IFATS and ISCT statement does not recommend to use term “stem cells”. The term “stromal cells” used in report instead “stem cells”. Stromal cells are defined as “connective tissue cells of any origin”.

The statement provides a guidelines for characterization of SVF and ASC, which includes viability, immunophenotype, proliferation and frequency (colony formation) and tri-lineage (adipo-, chondro-, osteo-) differentiation. The main focus is to compare adipose stromal cells in freshly isolated SVF versus cultured ASC and to propose a “quality criteria”, based on literature analysis. The authors draw a parallel between adipose SVF and bone marrow mononuclear cells as highly heterogeneous populations. ASC could be compared to bone marrow mesenchymal stromal cells (MSC). Because of these similarities, the authors proposed to adapt ISCT minimal criteria of MSC for adipose tissue. Importantly, the authors highlighted that cell culture can not resolve heterogeneity problem:

Although ASCs are less heterogeneous than SVF cells, they are by no means homogeneous.

Significant part of paper dedicated to immunophenotyping and identification of surface markers:

In the SVF, cells are identified phenotypically by the following markers: CD45-CD235a-CD31-CD34+. Added value may be provided by both a viability marker and the following surface antigens: CD13, CD73, CD90 and CD105.
In culture, ASCs retain markers in common with other mesenchymal stromal/stem cells (MSCs), including CD90, CD73, CD105, and CD44 and remain negative for CD45 and CD31.

The main difference between whole SVF and ASC is CD45 expression (no CD45+ cells in culture). CD34 expression is highly variable and greatly depends on cell isolation protocol, cell culture duration and conditions. To distinguish cultured ASC and MSC, the authors proposed to use CD36 (positive for ASC, negative for MSC) and CD106 (positive for MSC, negative for ASC).

We propose that a foundational phenotyping should include at least two negative markers and two positive markers in the same analysis.

This position statement is very good and timely initiative! Adherence to such recommendations could significantly improve quality of cell preparations from adipose tissue and decrease variability between labs and clinical facilities. Unlike ISCT minimal criteria for MSC, this guidelines addresses the difference between freshly isolated and ex vivo cultured (propagated) cells. It also partially addresses the question of “stemness” and definitions by recommendation to use “adipose stromal cells” term instead of “stem cells”. The report proposes to use new surface markers, based on recent updated literature. It is still lacking to address the issue of using adipose-derived cells as signaling cells for number of medical conditions, where surface markers expression and tri-lineage differentiation characteristics could be irrelevant to mechanisms of therapeutic action.

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