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Comparing the Regenerative Potential of SVF and MFAT - Which Adipose Tissue Preparation Comes out Top?

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Review of “Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

A recent STEM CELLS Translational Medicine article established the safety, feasibility, and potential effectiveness of single intra‐articular injections of micro‐fragmented adipose tissue (MFAT) [1, 2] as a treatment strategy for osteoarthritis when tested in a canine model [3]. As opposed to the enzymatic dissociation of adipose tissue followed by removal of adipocytes and collection of the remaining stromal vascular fraction (SVF) for regenerative applications, MFAT employs mechanical dissociation of adipose tissue to generate blood- and free lipid-free submillimeter cell clusters that have proven highly useful in the treatment of multiple indications, including incontinence, osteoarthritis, and chronic hindlimb ischemia.

To discover any differences to the regenerative potential between SVF and MFAT, researchers from the laboratory of Bruno Péault (University of California, USA/MRC Centre for Regenerative Medicine, Edinburgh, UK) compared perivascular cell distribution and in vitro protein secretion as a means of scoring their regenerative potential. Reporting in STEM CELLS Translational Medicine, Vezzani et al. now establish that adipose tissue fragmentation preserves a high perivascular cell content, while enzymatic dissociation negatively influences growth factor and cytokine secretion [4].

Immunohistochemical analysis of MFAT clusters demonstrated the presence of capillaries and microvessels between adipocytes as well as pericytes wrapped around endothelial cells, similar to intact adipose tissue. In confirmation of previous observations [2, 5], subsequent comparisons of adipose tissue preparations indicated an enrichment for NG2- or PDGFRβ-expressing pericytes at the expense of adventitial cells (connective tissue) in MFAT (~34% pericytes) when compared to SVF (~8.5%), suggesting the preservation of the perivascular niche.  Furthermore, MFAT released a significantly higher number and level of growth factors and cytokines involved in tissue repair and regeneration. Overexpressed growth factors included angiogenin, hepatocyte growth factor, leptin, PDGF-AB/BB, placental growth factor, thrombospondin 2, and TIMP4, while overexpressed cytokines included adiponectin, CD14, CD31, IGFBP‐2, IL1RA, M‐CSF, PDGF-AA, RANTES, TNF‐α, and uPAR, with many of these factors playing critical roles in angiogenesis and immunomodulation. 

Overall, this comparison of SVF and MFAT suggests that fragmentation comes out on top when compared to enzymatic dissociation, although further animal model studies will be required to confirm the superior regenerative potential of MFAT.

For more on the regenerative potential of adipose tissue, whatever the preparation strategy, stay tuned to the Stem Cells Portal!

References

  1. Ceserani V, Ferri A, Berenzi A, et al., Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vascular Cell 2016;8:3.
  2. Bianchi F, Maioli M, Leonardi E, et al., A New Nonenzymatic Method and Device to Obtain a Fat Tissue Derivative Highly Enriched in Pericyte-Like Elements by Mild Mechanical Forces from Human Lipoaspirates. Cell Transplantation 2013;22:2063-2077.
  3. Zeira O, Scaccia S, Pettinari L, et al., Intra-Articular Administration of Autologous Micro-Fragmented Adipose Tissue in Dogs with Spontaneous Osteoarthritis: Safety, Feasibility, and Clinical Outcomes. STEM CELLS Translational Medicine 2018;7:819-828.
  4. Vezzani B, Shaw I, Lesme H, et al., Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction. STEM CELLS Translational Medicine 2018;7:876-886.
  5. Ceserani V, Ferri A, Berenzi A, et al., Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells. Vascular Cell 2016;8:3.