Implantable patches assembled with mesenchymal stem cells and gelatin/silk fibroin composite microspheres for the treatment of traumatic optic neuropathy
Source abstract
Abstract
Abstract The therapeutic benefits of transplanting mesenchymal stem cells (MSCs) to the injury site of traumatic optic neuropathy (TON) represents a crucial, yet unresolved question, the answer to which may facilitate development of innovative therapies for TON, a frustrating disease with no effective treatment. Herein, we address this issue by showing that MSC transplantation to the injury site is able to promote optic nerve regeneration in terms of retinal ganglion cell survival and axon regeneration using MSC@MS, implantable patches assembled with MSCs and gelatin/silk fibroin composite microspheres, which integrate 3D culture and trypsin-free harvesting, and can increase in vivo retention of transplanted MSCs. In contrast, conventional bolus injection of MSC suspension is not potent enough to produce significant benefits. We also show MSCs in MSC@MS demonstrate superior gene expression profiles over monolayer culture after IGF-1 stimulation. In future study, microspheres in MSC@MS can further be harnessed to deliver therapeutic cargoes that boost the potency of MSCs or treat TON synergistically with MSCs, making MSC@MS a versatile platform to develop tailored MSC-based therapies for TON.
Source: openaire · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Corneal Surgery and Treatments · Nerve injury and regeneration · Cellular Mechanics and Interactions
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (50)
Show source-provided references
1. Traumatic optic neuropathy
2. A controlled impact of optic nerve as a new model of traumatic optic neuropathy in mouse10.1167/iovs.18-24773 ↗
3. Exploiting mTOR signaling: a novel translatable treatment strategy for traumatic optic neuropathy?10.1167/iovs.13-12803 ↗
4. Zinc chelation and Klf9 knockdown cooperatively promote axon regeneration after optic nerve injury10.1016/j.expneurol.2017.10.025 ↗
5. Optic nerve regeneration: considerations on treatment of acute optic neuropathy and end-stage disease10.1007/s40135-019-00194-0 ↗
6. Direct targeting of the mouse optic nerve for therapeutic delivery10.1016/j.jneumeth.2018.10.038 ↗
7. Promoting optic nerve regeneration10.1016/j.preteyeres.2012.06.005 ↗
8. Neuroinflammation triggered by β-glucan/dectin-1 signaling enables CNS axon regeneration10.1073/pnas.1423221112 ↗
9. Mobile zinc increases rapidly in the retina after optic nerve injury and regulates ganglion cell survival and optic nerve regeneration10.1073/pnas.1616811114 ↗
10. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons10.1038/nn.4340 ↗
11. Optic nerve regeneration after crush remodels the injury site: molecular insights from imaging mass spectrometry10.1167/iovs.17-22509 ↗
12. Effective modulation of CNS inhibitory microenvironment using bioinspired hybrid-nanoscaffold-based therapeutic interventions
13. Mesenchymal stem cell perspective: cell biology to clinical progress10.1038/s41536-019-0083-6 ↗
14. Manufacturing of primed mesenchymal stromal cells for therapy10.1038/s41551-018-0325-8 ↗
15. Intravitreal injections of neurotrophic factors secreting mesenchymal stem cells are neuroprotective in rat eyes following optic nerve transection10.1167/iovs.09-4310 ↗
16. Human Wharton's jelly mesenchymal stem cells protect axotomized rat retinal ganglion cells via secretion of anti-inflammatory and neurotrophic factors10.1038/s41598-018-34527-z ↗
17. Biomaterials that promote cell-cell interactions enhance the paracrine function of MSCs10.1016/j.biomaterials.2017.06.019 ↗
18. Preconditioning of bone marrow-derived mesenchymal stem cells with N-acetyl-L-cysteine enhances bone regeneration via reinforced resistance to oxidative stress10.1016/j.biomaterials.2018.08.055 ↗
19. Multilineage potential of bone-marrow-derived mesenchymal stem cell cell sheets: implications for tissue engineering10.1089/ten.tea.2009.0501 ↗
20. Reactive oxygen species scavenging and biodegradable peptide hydrogel as 3D culture scaffold for cardiomyocytes10.1021/acsbiomaterials.0c00340 ↗
21. Thermoresponsive magnetic colloidal gels via surface-initiated polymerisation from functional microparticles10.1039/C5TB01739D ↗
22. PLGA hybrid porous microspheres as human periodontal ligament stem cell delivery carriers for periodontal regeneration10.1016/j.cej.2021.129703 ↗
23. Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation10.1073/pnas.1819415116 ↗
24. Gelatin-CaO2/SAP/PLGA composite scaffold enhances the reparation of critical-sized cranial defects by promoting seed cell survival
25. Biofabrication and characterization of alginate dialdehyde-gelatin microcapsules incorporating bioactive glass for cell delivery application10.1002/mabi.202000138 ↗
26. Transmembrane collagen receptors10.1146/annurev-cellbio-092910-154013 ↗
27. Structurally and functionally optimized silk-fibroin–gelatin scaffold using 3D printing to repair cartilage injury in vitro and in vivo10.1002/adma.201701089 ↗
28. Preparation and the hemostatic property study of porous gelatin microspheres both in vitro and in vivo10.1016/j.colsurfb.2019.110641 ↗
29. Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation10.1073/pnas.1819415116 ↗
30. Challenges for mesenchymal stromal cell therapies10.1126/scitranslmed.aat2189 ↗
31. Substrate stiffness affects the immunosuppressive and trophic function of hMSCs via modulating cytoskeletal polymerization and tension10.1039/C9BM01202H ↗
32. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets10.1038/s41467-019-09234-6 ↗
33. Lens injury stimulates axon regeneration in the mature rat optic nerve10.1523/JNEUROSCI.20-12-04615.2000 ↗
34. Progress of gelatin-based microspheres (GMSs) as delivery vehicles of drug and cell10.1016/j.msec.2021.111949 ↗
35. Silk fibroin/gelatin microcarriers as scaffolds for bone tissue engineering10.1016/j.msec.2019.110116 ↗
36. Harnessing macrophage-mediated degradation of gelatin microspheres for spatiotemporal control of BMP2 release10.1016/j.biomaterials.2018.01.040 ↗
37. Control of silk microsphere formation using polyethylene glycol (PEG)10.1016/j.actbio.2016.05.019 ↗
38. Cytoprotective role of vitamin E in porcine adipose-tissue-derived mesenchymal stem cells against hydrogen-peroxide-induced oxidative stress10.1007/s00441-018-2857-3 ↗
39. Biomaterials for enhancing CNS repair10.1007/s12975-016-0470-x ↗
40. Cellular hydrogel biopaper for patterned 3D cell culture and modular tissue reconstruction10.1002/adhm.201200158 ↗
41. Bioengineering strategies to accelerate stem cell therapeutics10.1038/s41586-018-0089-z ↗
42. Preparation of stem cell aggregates with gelatin microspheres to enhance biological functions10.1016/j.actbio.2011.04.013 ↗
43. Enhanced biological functions of human mesenchymal stem-cell aggregates incorporating E-cadherin-modified PLGA microparticles10.1002/adhm.201600114 ↗
44. Hydrogel microparticles for biomedical applications10.1038/s41578-019-0148-6 ↗
45. Synthetic niche to modulate regenerative potential of MSCs and enhance skeletal muscle regeneration10.1016/j.biomaterials.2016.05.009 ↗
46. Stem cell-mediated muscle regeneration is enhanced by local isoform of insulin-like growth factor 110.1073/pnas.0303792101 ↗
47. The RNA binding protein RBPMS is a selective marker of ganglion cells in the mammalian retina10.1002/cne.23521 ↗
48. A new neutrophil subset promotes CNS neuron survival and axon regeneration10.1038/s41590-020-00813-0 ↗
49. Shattering barriers toward clinically meaningful MSC therapies10.1126/sciadv.aba6884 ↗
50. Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids10.1038/srep04645 ↗