Three-dimensional-cultured MSC-derived exosome with hydrogel for cerebral ischemia repair
Source abstract
Abstract
Microglia-mediated neuroinflammatory response, one of the most essential pathological processes of cerebral ischemia-reperfusion (I/R) injury, is acknowledged as the main factors leading to poor prognosis of cerebral ischemia. Exosome derived from mesenchymal stem cell (MSC-Exo) exhibits neuroprotective functions by reducing cerebral ischemia-induced neuroinflammatory response and promoting angiogenesis. However, MSC-Exo has disadvantages such as insufficient targeting capability and low production, which limits their clinical applications. Here, we fabricated gelatin methacryloyl (GelMA) hydrogel for three-dimensional (3D) culture of MSCs. It is indicated that 3D environment could simulate the biological niches of MSCs, thereby significantly increasing the cell stemness of MSCs and improving the yield of MSCs-derived exosomes (3D-Exo). In this study, we utilized the modified Longa method to induce middle cerebral artery occlusion (MCAO) model. Additionally, in vitro and in vivo studies were conducted to interrogate the mechanism of the stronger neuroprotective effect of 3D-Exo. Furthermore, the administration of 3D-Exo in MCAO model could promote neovascularization in infarct region and result in a significant suppression of inflammatory response. This study proposed an exosome-based targeting delivery system for cerebral ischemia and provided a promising strategy for efficient and large-scale production of MSC-Exo.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Extracellular vesicles in disease · Neuroinflammation and Neurodegeneration Mechanisms · MicroRNA in disease regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (57)
Show source-provided references
1. Effect of a quality improvement intervention on adherence to therapies for patients with acute ischemic stroke and transient ischemic attack: a cluster randomized clinical trial10.1001/jamaneurol.2019.1012 ↗
2. Neutrophil membrane-derived nanovesicles alleviate inflammation to protect mouse brain injury from ischemic stroke
3. Theanine attenuates hippocampus damage of rat cerebral ischemia-reperfusion injury by inhibiting ho-1 expression and activating erk1/2 pathway10.1016/j.lfs.2019.117160 ↗
4. Trem-1 exacerbates neuroinflammatory injury via nlrp3 inflammasome-mediated pyroptosis in experimental subarachnoid hemorrhage10.1007/s12975-020-00840-x ↗
5. Genistein-3'-sodium sulfonate attenuates neuroinflammation in stroke rats by down-regulating microglial m1 polarization through α7nachr-nf-κb signaling pathway10.7150/ijbs.56800 ↗
6. Il (interleukin)-15 bridges astrocyte-microglia crosstalk and exacerbates brain injury following intracerebral hemorrhage10.1161/STROKEAHA.119.028638 ↗
7. Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke10.1016/j.biomaterials.2020.119942 ↗
8. Exosomes and ectosomes in intercellular communication10.1016/j.cub.2018.01.059 ↗
9. Mesenchymal stem cell-based therapy as an alternative to the treatment of acute respiratory distress syndrome: current evidence and future perspectives10.3390/ijms22157850 ↗
10. Heterochirality and halogenation control phe-phe hierarchical assembly10.1021/acsnano.0c06041 ↗
11. Tuning hydrogels by mixing dynamic cross-linkers: enabling cell-instructive hydrogels and advanced bioinks
12. Murine bone marrow-derived mesenchymal stem cells as vehicles for interleukin-12 gene delivery into Ewing sarcoma tumors10.1002/cncr.24013 ↗
13. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells10.1016/j.actbio.2017.08.005 ↗
14. Tailor-made semiconducting polymers for second near-infrared photothermal therapy of orthotopic liver cancer10.1021/acsnano.9b03910 ↗
15. Exosomes harbor b cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity10.1038/s41467-018-08109-6 ↗
16. Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis10.1002/term.2947 ↗
17. Dose-effect relationship and molecular mechanism by which bmsc-derived exosomes promote peripheral nerve regeneration after crush injury10.1186/s13287-020-01872-8 ↗
18. Rab11b-mediated integrin recycling promotes brain metastatic adaptation and outgrowth10.1038/s41467-020-16832-2 ↗
19. Reversible middle cerebral artery occlusion without craniectomy in rats10.1161/01.STR.20.1.84 ↗
20. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice10.1186/s12974-018-1153-1 ↗
21. Electroacupuncture treatment improves neurological function associated with regulation of tight junction proteins in rats with cerebral ischemia reperfusion injury10.1155/2014/989340 ↗
22. Neuroprotective effect of mesenchymal stromal cell-derived extracellular vesicles against cerebral ischemia-reperfusion-induced neural functional injury: a pivotal role for ampk and jak2/stat3/nf-κb signaling pathway modulation10.2147/DDDT.S248892 ↗
23. Melatonin ameliorates cerebral ischemia/reperfusion injury through sirt3 activation10.1016/j.lfs.2019.117036 ↗
24. Adipose-derived mesenchymal stem cell-derived exosomes alleviate overwhelming systemic inflammatory reaction and organ damage and improve outcome in rat sepsis syndrome
25. Preactivated and disaggregated shape-changed platelets protected against acute respiratory distress syndrome complicated by sepsis through inflammation suppression10.1097/SHK.0000000000000617 ↗
26. Mesenchymal stem cell-derived exosomes as a nanotherapeutic agent for amelioration of inflammation-induced astrocyte alterations in mice10.7150/thno.33872 ↗
27. Exosomes/mirnas as mediating cell-based therapy of stroke10.3389/fncel.2014.00377 ↗
28. Neurogenesis after stroke: a therapeutic perspective10.1007/s12975-020-00841-w ↗
29. Microglial responses to brain injury and disease: functional diversity and new opportunities10.1007/s12975-020-00857-2 ↗
30. Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro10.1186/s13287-017-0531-4 ↗
31. Impairment of an endothelial nad(+)-h(2)s signaling network is a reversible cause of vascular aging10.1016/j.cell.2018.02.008 ↗
32. Neuroregeneration and functional recovery after stroke: advancing neural stem cell therapy toward clinical application10.4103/1673-5374.286955 ↗
33. Chronic exposure to subtherapeutic antibiotics aggravates ischemic stroke outcome in mice10.1016/j.ebiom.2017.09.002 ↗
34. Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro10.1089/scd.2014.0316 ↗
35. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species10.1186/s13287-015-0116-z ↗
36. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappab signaling10.1002/stem.2298 ↗
37. Bioengineering approaches for the advanced organoid research10.1002/adma.202007949 ↗
38. Controlling the release of small, bioactive proteins via dual mechanisms with therapeutic potential10.1002/adhm.201700713 ↗
39. Gelatin-methacryloyl hydrogels: towards biofabrication-based tissue repair10.1016/j.tibtech.2016.01.002 ↗
40. Characterizing the effects of synergistic thermal and photo-cross-linking during biofabrication on the structural and functional properties of gelatin methacryloyl (gelma) hydrogels10.1021/acsbiomaterials.1c00635 ↗
41. Capturing magnesium ions via microfluidic hydrogel microspheres for promoting cancellous bone regeneration10.1021/acsnano.1c02147 ↗
42. Promoting 3d neuronal differentiation in hydrogel for spinal cord regeneration10.1016/j.colsurfb.2020.111214 ↗
43. Exosomes produced from 3d cultures of mscs by tangential flow filtration show higher yield and improved activity10.1016/j.ymthe.2018.09.015 ↗
44. Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies10.7150/ijbs.41637 ↗
45. Comparative analysis of mesenchymal stem cell cultivation in fetal calf serum, human serum, and platelet lysate in 2d and 3d systems
46. Bioactive nanoengineered hydrogels for bone tissue engineering: a growth-factor-free approach10.1021/nn507488s ↗
47. Three-dimensional culture of mscs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury10.1186/s13287-020-01719-2 ↗
48. Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells10.1038/s41598-018-19211-6 ↗
49. Comparison of immunosuppressive and angiogenic properties of human amnion-derived mesenchymal stem cells between 2d and 3d culture systems10.1155/2019/7486279 ↗
50. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2d and 3d conditions improves functional recovery in rats after traumatic brain injury10.1016/j.neuint.2016.08.003 ↗
51. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2d and 3d conditions improves functional recovery in rats after traumatic brain injury10.1016/j.neuint.2016.08.003 ↗
52. 3d cellular architecture affects microRNA and protein cargo of extracellular vesicles10.1002/advs.201800948 ↗
53. Interleukin 1 receptor-like 1 (il1rl1) promotes airway bacterial and viral infection and inflammation10.1128/IAI.00340-19 ↗
54. Synergistic effect of pcpe1 and sfrp2 on the processing of procollagens via bmp110.1002/1873-3468.13291 ↗
55. Neuroprotective effects of natural compounds on lps-induced inflammatory responses in microglia
56. Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms10.1016/j.phrs.2020.105224 ↗
57. Developmental alterations in huntington's disease neural cells and pharmacological rescue in cells and mice10.1038/nn.4532 ↗