Autologous adipose tissue is used for tissue repletion and/or regeneration as an intact lipoaspirate or as enzymatically derived stromal vascular fraction, which may be first cultured into mesenchymal stem cells. Alternatively, transplant of autologous adipose tissue mechanically fragmented into sub-millimetre clusters has recently showed remarkable efficacy in diverse therapeutic indications. To document the biologic basis of the regenerative potential of micro-fragmented adipose tissue, we have first analysed the distribution of perivascular presumptive mesenchymal stem cells 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 mesenchymal stem cells 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 stromal vascular fraction using secretome arrays. In culture, micro-fragmented adipose tissue releases many more growth factors and cytokines involved in tissue repair and regeneration, noticeably via angiogenesis, compared to isogenic stromal vascular fraction. Therefore, we suggest that the efficient tissue repair/regeneration observed after transplantation of micro-fragmented adipose tissue is due to the secretory ability of the intact perivascular niche.