Higher Pericyte Content and Secretory Activity of Microfragmented Human Adipose Tissue Compared to Enzymatically Derived Stromal Vascular Fraction

Abstract

Autologous adipose tissue is used for tissue repletion and/or regeneration as an intact lipoaspirate or as enzymatically derived stromal vascular fraction (SVF), which may be first cultured into mesenchymal stem cells (MSCs). Alternatively, transplant of autologous adipose tissue mechanically fragmented into submillimeter clusters has recently showed remarkable efficacy in diverse therapeutic indications. To document the biologic basis of the regenerative potential of microfragmented adipose tissue, we first analyzed the distribution of perivascular presumptive MSCs in adipose tissue processed with the Lipogems technology, observing a significant enrichment in pericytes, at the expense of adventitial cells, as compared to isogenic enzymatically processed lipoaspirates. The importance of MSCs as trophic and immunomodulatory cells, due to the secretion of specific factors, has been described. Therefore, we investigated protein secretion by cultured adipose tissue clusters or enzymatically derived SVF using secretome arrays. In culture, microfragmented adipose tissue releases many more growth factors and cytokines involved in tissue repair and regeneration, noticeably via angiogenesis, compared to isogenic SVF. Therefore, we suggest that the efficient tissue repair/regeneration observed after transplantation of microfragmented adipose tissue is due to the secretory ability of the intact perivascular niche. Stem Cells Translational Medicine 2018;7:876–886

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

“…In fact, previous studies have shown that the secretome of cultured intact adipose tissue has superior anti-inflammatory properties compared to the secretome of cultured stromal vascular fraction (SVF), which has been enzymatically digested and lacks certain cell types, such as adipocytes. [75] These results indicate that the secretome may be more functional when derived from an intact adipose environment compared to adipose tissue that has been digested and cultured. In this study, the physicochemical and anti-inflammatory properties of patient lipoaspirate-derived BiNPs were studied.…”

“…This approach based on limited manipulation could also preserve unique properties that are not present in an in vitro expanded environment. In fact, previous studies have shown that the secretome of cultured intact adipose tissue has superior anti‐inflammatory properties compared to the secretome of cultured stromal vascular fraction (SVF), which has been enzymatically digested and lacks certain cell types, such as adipocytes 75. These results indicate that the secretome may be more functional when derived from an intact adipose environment compared to adipose tissue that has been digested and cultured.…”

Functional Outcomes Following Microfragmented Adipose Tissue Versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis

“…Ceserani et al note that estimation of MSC number per milliliter of MFAT has proven to be technically difficult [44]. However, MFAT is rich in microvessels and pericytes, which are immature MSC progenitors [44,45]. Multiple investigators have clearly documented that pericytes give rise to MSCs [46,47].…”

“…Previous data have shown that the majority of MSCs cultured from MFAT are of pericyte origin [44]. In addition, MFAT is also rich in angiogenic, anti-inflammatory, and immunomodulatory growth factors and cytokines such as IL1-RA, placental growth factor, PDGF, dipeptidyl peptidase 4, Ang-1, Ang-2, matrix metallopeptidase (MMP)-7, MMP-9, adiponectin, and HGF [44,45]. MFAT has further anti-inflammatory properties through blocking monocyte inflammatory functions [44].…”

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“…Autologous adipose tissue has been used as intact lipo-aspirate, enzymatically derived Stromal Vascular Fraction (SVF) or Micro Fragmented Fat (MFAT). Vezzani et al, [18] has demonstrated that the "regenerative properties" of these three methods are quite different; with the MFAT preparations being significantly more productive in the release of grow factor and cytokines concomitant with notably superior effects on repairing tissues, induction and modification of immunomodulatory activity and in supporting vascular angiogenesis.…”