PloS one, 2019-10, Vol.14 (10), p.e0222093
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Investigating the potential of the secretome of mesenchymal stem cells derived from sickle cell disease patients
- Ist Teil von
- PloS one, 2019-10, Vol.14 (10), p.e0222093
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Sickle cell disease (SCD) is a monogenic red cell disorder associated with multiple vascular complications, microvessel injury and wound-healing deficiency. Although stem cell transplantation with bone marrow-derived mesenchymal stem cells (BMSC) can promote wound healing and tissue repair in SCD patients, therapeutic efficacy is largely dependent on the paracrine activity of the implanted BM stromal cells. Since in vitro expansion and culture conditions are known to modulate the innate characteristics of BMSCs, the present study investigated the effects of normoxic and hypoxic cell-culture preconditioning on the BMSC secretome, in addition to the expression of paracrine molecules that induce angiogenesis and skin regeneration. BMSCs derived from SCD patients were submitted to culturing under normoxic (norCM) and hypoxic (hypoCM) conditions. We found that hypoxically conditioned cells presented increased expression and secretion of several well-characterized trophic growth factors (VEGF, IL8, MCP-1, ANG) directly linked to angiogenesis and tissue repair. The hypoCM secretome presented stronger angiogenic potential than norCM, both in vitro and in vivo, as evidenced by HUVEC proliferation, survival, migration, sprouting formation and in vivo angiogenesis. After local application in a murine wound-healing model, HypoCM showed significantly improved wound closure, as well as enhanced neovascularization in comparison to untreated controls. In sum, the secretome of hypoxia-preconditioned BMSC has increased expression of trophic factors involved in angiogenesis and skin regeneration. Considering that these preconditioned media are easily obtainable, this strategy represents an alternative to stem cell transplantation and could form the basis of novel therapies for vascular regeneration and wound healing in individuals with sickle cell disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0222093Titel-ID: cdi_plos_journals_2310643941
- Format
- –
- Schlagworte
- Analysis, Anemia, Sickle Cell - genetics, Anemia, Sickle Cell - pathology, Angiogenesis, Animals, Biology and Life Sciences, Biomarkers, Bone healing, Bone marrow, Bone Marrow Cells - metabolism, Bone Marrow Cells - pathology, Bone marrow transplantation, Care and treatment, Cell culture, Cell Hypoxia - genetics, Cell Movement - genetics, Cell Proliferation - genetics, Complications, Culture Media, Conditioned - pharmacology, Endothelial growth factors, Gene Expression Regulation, Developmental - genetics, Growth factors, Heart attacks, Human Umbilical Vein Endothelial Cells, Humans, Hypoxia, Interleukin 8, Internal medicine, Medicine, Medicine and Health Sciences, Mesenchymal Stem Cell Transplantation, Mesenchymal stem cells, Mesenchymal Stem Cells - metabolism, Mesenchymal Stem Cells - pathology, Mesenchyme, Mice, Monocyte chemoattractant protein 1, Neovascularization, Neovascularization, Physiologic - genetics, Novels, Paracrine signalling, Preconditioning, Regeneration, Regeneration - genetics, Repair, Secretome, Sickle cell anemia, Sickle cell disease, Skin, Skin - growth & development, Skin - metabolism, Stem cell transplantation, Stem cells, Stromal cells, Surgery, Surgical implants, Tissue engineering, Transplantation, Trophic factors, Ulcers, Vascular endothelial growth factor, Vascularization, Wound care, Wound healing, Wound Healing - genetics