The angiogenic potential of CD271+ human adipose tissue-derived mesenchymal stem cells

Abstract

Background Autologous fat grafting is often a crucial aspect of reconstructive and aesthetic surgeries, yet poor graft retention is a major issue with this technique. Enriching fat grafts with adipose tissue-derived mesenchymal stem cells (AD-MSCs) improves graft survival—however, AD-MSCs represent a heterogeneous population. Selection of subpopulations of AD-MSCs would allow the targeting of specific AD-MSCs that may benefit fat graft survival more than the general AD-MSC population. Methods Human AD-MSCs were selected for the surface marker CD271 using magnetic-activated cell sorting and compared to the CD271 negative phenotype. These subpopulations were analysed for gene expression using Real-Time qPCR and RNA sequencing; surface marker characteristics using immunostaining; ability to form tubules when cultured with endothelial cells; and gene and protein expression of key angiogenic mediators when cultured with ex-vivo adipose tissue. Results Human AD-MSCs with the surface marker CD271 express angiogenic genes at higher levels, and inflammatory genes at lower levels, than the CD271− AD-MSC population. A greater proportion of CD271+ AD-MSCs also possess the typical complement of stem cell surface markers and are more likely to promote effective neoangiogenesis, compared to CD271− AD-MSCs. Conclusion Enriching grafts with the CD271+ AD-MSC subpopulation holds potential for the improvement of reconstructive and aesthetic surgeries involving adipose tissue.

Single-cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia

“…In previous reports, CD271 + cells from BM and AT showed reduced surface CD271 expression during early in vitro passaging but maintained 0.5%–5% of CD271-expressing cells upon further passaging. 38 , 40 We confirmed that approximately 5%–10% of our sorted AT-CD271 + cells retained surface CD271 protein expression after eight passages ( Figure S3 C).…”

Single cell transcriptomics identifies adipose tissue CD271+ progenitors for enhanced angiogenesis in limb ischemia

“…Interestingly, previous demonstrations that CD271 + cell/HUVEC coculture, but not conditioned medium, could enhance the tube formation of HUVECs, suggest the importance of cell-to-cell interactions between CD271 + progenitors and target cells. 51,52 In our xenograft model, we observed CD271 + progenitors were surrounding capillaries and labeled by perfused lectin as with capillaries (Figure 4B-C and Figure S3A). This indicates the close proximities between "leaky" capillaries and engrafted cell grafts.…”

“…There is a report demonstrating that CD271 + progenitors secreted angiogenic factors in vitro . 52 However, limited angiogenesis was concomitantly observed in a mouse model of CD271 + cell injection for cartilage repair. 53 Based on our present results, CD271 + progenitors could exhibit angiogenic capacity specifically in ischemic-type diseases.…”

Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations

“…Interestingly, the MSCs express some neural development related genes and some of them have been identified as MSC markers, such as CSPG4 (chondroitin sulfate proteoglycan 4) [228][229][230], GD2 (Disialoganglioside) [231], CD271 [232][233][234][235][236][237][238], and Nestin [239][240][241][242][243]. Whether the expression of neuron related genes indicates the dedifferentiated state of MSCs or potential interactions between MSCs and neurons remains unclear and needs further investigation.…”