d89f8c6d83625a1ea8be98e682e293e2 296599.pdf f371619513f0cc94ee74938424b36ef7bc7619da 296599.pdf 7f3fb1efa15a26ae28b253c211d3aab79a8605a15d2bfcf946ca742829c3b7f9 296599.pdf Title: Adipose-Derived Stem Cells to Treat Ischemic Diseases: The Case of Peripheral Artery Disease Subject: Critical limb ischemia incidence and prevalence have increased over the years. However, there are no successful treatments to improve quality of life and to reduce the risk of cardiovascular and limb events in these patients. Advanced regenerative therapies have focused their interest on the generation of new blood vessels to repair tissue damage through the use of stem cells. One of the most promising sources of stem cells with high potential in cell-based therapy is adipose-derived stem cells (ASCs). ASCs are adult mesenchymal stem cells that are relatively abundant and ubiquitous and are characterized by a multilineage capacity and low immunogenicity. The proangiogenic benefits of ASCs may be ascribed to: (a) paracrine secretion of proangiogenic molecules that may stimulate angiogenesis; (b) secretion of microvesicles/exosomes that are also considered as a novel therapeutic prospect for treating ischemic diseases; and (c) their differentiation capability toward endothelial cells (ECs). Although we know the proangiogenic effects of ASCs, the therapeutic efficacy of ASCs after transplantation in peripheral artery diseases patients is still relatively low. In this review, we evidence the potential therapeutic use of ASCs in ischemic regenerative medicine. We also highlight the main challenges in the differentiation of these cells into functional ECs. However, significant efforts are still needed to ascertain relevant transcription factors, intracellular signaling and interlinking pathways in endothelial differentiation. Keywords: peripheral artery disease; critical limb ischemia; adipose-derived stem cells; cell therapy; angiogenesis; ASC differentiation Author: Gemma Arderiu, Anna Civit-Urgell and Lina Badimon Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Sat Nov 25 10:11:43 2023 CET ModDate: Sat Nov 25 10:15:42 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1479635 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- OCDMSW+VnURWPalladioL Type 1 Custom yes yes no 10 0 NJDESG+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 RJAOAD+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 MJRCIP+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 42 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 45 0 PDTLUH+CMSY10 Type 1 Builtin yes yes no 67 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 79 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 83 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 87 0 LWLIVD+EURM10 Type 1 Builtin yes yes no 105 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 113 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 117 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 121 0 BCDHEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 125 0 BCDIEE+CambriaMath CID TrueType Identity-H yes yes yes 132 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 155 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 159 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 163 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-07-17 02:36:55 CEST RepresentationInformation: 296599.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-07-16 13:16:31 CEST Size: 1479635 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 524 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Peripheral Artery Disease Destination: section.2 Item: Title: Critical Limb Ischemia Destination: section.3 Item: Title: Therapeutic Angiogenesis Destination: section.4 Item: Title: Stem Cells: Adipose Tissue-Derived Stem Cells Destination: section.5 Item: Title: The Importance of ASCs Secretome and Its Effects on Cellular Mechanisms Destination: section.6 Item: Title: ASCs Differentiation into an Endothelial-like Phenotype to Increase Their Angiogenic Potential Destination: section.7 Item: Title: Signaling Pathways Involved in ASCs Differentiation into an Endothelial-like Phenotype Destination: section.8 Item: Title: Other Cells with Angiogenic Potential Destination: section.9 Item: Title: Conclusions and Future Perspectives Destination: section.10 Item: Title: References Destination: section.11 Info: Title: Adipose-Derived Stem Cells to Treat Ischemic Diseases: The Case of Peripheral Artery Disease Author: Gemma Arderiu, Anna Civit-Urgell and Lina Badimon Subject: Critical limb ischemia incidence and prevalence have increased over the years. However, there are no successful treatments to improve quality of life and to reduce the risk of cardiovascular and limb events in these patients. Advanced regenerative therapies have focused their interest on the generation of new blood vessels to repair tissue damage through the use of stem cells. One of the most promising sources of stem cells with high potential in cell-based therapy is adipose-derived stem cells (ASCs). ASCs are adult mesenchymal stem cells that are relatively abundant and ubiquitous and are characterized by a multilineage capacity and low immunogenicity. The proangiogenic benefits of ASCs may be ascribed to: (a) paracrine secretion of proangiogenic molecules that may stimulate angiogenesis; (b) secretion of microvesicles/exosomes that are also considered as a novel therapeutic prospect for treating ischemic diseases; and (c) their differentiation capability toward endothelial cells (ECs). Although we know the proangiogenic effects of ASCs, the therapeutic efficacy of ASCs after transplantation in peripheral artery diseases patients is still relatively low. In this review, we evidence the potential therapeutic use of ASCs in ischemic regenerative medicine. We also highlight the main challenges in the differentiation of these cells into functional ECs. However, significant efforts are still needed to ascertain relevant transcription factors, intracellular signaling and interlinking pathways in endothelial differentiation. 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