Controlled Release of Neurotrophin-3 and Platelet-derived Growth Factor from Fibrin Scaffolds Containing Neural Progenitor Cells Enhances Survival and Differentiation into Neurons in a Subacute Model of SCI

Overview

Journal Cell Transplant

Specialties Cell Biology
General Surgery

Date 2009 Oct 13

PMID 19818206

Citations 66

Authors

Philip J Johnson

Alexander Tatara

Alicia Shiu

Shelly E Sakiyama-Elbert

Affiliations

Soon will be listed here.

Abstract

A consistent problem with stem/neural progenitor cell transplantation following spinal cord injury (SCI) is poor cell survival and uncontrolled differentiation following transplantation. The current study evaluated the feasibility of enhancing embryonic stem cell-derived neural progenitor cell (ESNPC) viability and directing their differentiation into neurons and oligodendrocytes by embedding the ESNPCs in fibrin scaffolds containing growth factors (GF) and a heparin-binding delivery system (HBDS) in a subacute rat model of SCI. Mouse ESNPCs were generated from mouse embryonic stem cells (ESCs) using a 4-/4+ retinoic acid (RA) induction protocol. The ESNPCs were then transplanted as embryoid bodies (EBs, 70% neural progenitor cells) into the subacute model of SCI. ESNPCs (10 EBs per animal) were implanted directly into the SCI lesion, encapsulated in fibrin scaffolds, encapsulated in fibrin scaffolds containing the HBDS, neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF), or encapsulated in fibrin scaffolds with NT-3 and PDGF with no HBDS. We report here that the combination of the NT-3, PDGF, and fibrin scaffold (with or without HBDS) enhanced the total number of ESNPCs present in the spinal cord lesion 2 weeks after injury. In addition, the inclusion of the HBDS with growth factor resulted in an increase in the number of ESNPC-derived NeuN-positive neurons. These results demonstrate the ability of fibrin scaffolds and the controlled release of growth factors to enhance the survival and differentiation of neural progenitor cells following transplantation into a SCI model.

Citing Articles

Contractile and Genetic Characterization of Cardiac Constructs Engineered from Human Induced Pluripotent Stem Cells: Modeling of Tuberous Sclerosis Complex and the Effects of Rapamycin.

Sidorov V, Sidorova T, Samson P, Reiserer R, Britt C, Neely M Bioengineering (Basel). 2024; 11(3).

PMID: 38534508 PMC: 10968530. DOI: 10.3390/bioengineering11030234.

Combinatorial strategies for cell transplantation in traumatic spinal cord injury.

Jagrit V, Koffler J, Dulin J Front Neurosci. 2024; 18:1349446.

PMID: 38510468 PMC: 10951004. DOI: 10.3389/fnins.2024.1349446.

The Effect of Collagen and Fibrin Hydrogels Encapsulated with Adipose Tissue Mesenchymal Stem Cell-Derived Exosomes for Treatment of Spinal Cord Injury in a Rat Model.

Afsartala Z, Hadjighassem M, Shirian S, Ebrahimi-Barough S, Gholami L, Parsamanesh G Iran J Biotechnol. 2024; 21(3):e3505.

PMID: 38344702 PMC: 10858360. DOI: 10.30498/ijb.2023.362229.3505.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment.

Liu S, Liu B, Li Q, Zheng T, Liu B, Li M Neural Regen Res. 2023; 19(2):440-446.

PMID: 37488909 PMC: 10503599. DOI: 10.4103/1673-5374.379049.

Optimizing Differentiation Protocols for Producing Dopaminergic Neurons from Human Induced Pluripotent Stem Cells for Tissue Engineering Applications: Supplementary Issue: Stem Cell Biology.

Robinson M, Yau S, Sun L, Gabers N, Bibault E, Christie B Biomark Insights. 2023; 10 Suppl 1:61-70.

PMID: 36876191 PMC: 9980910. DOI: 10.4137/BMI.S20064.

References

Willerth S, Arendas K, Gottlieb D, Sakiyama-Elbert S . Optimization of fibrin scaffolds for differentiation of murine embryonic stem cells into neural lineage cells. Biomaterials. 2006; 27(36):5990-6003. PMC: 1794024. DOI: 10.1016/j.biomaterials.2006.07.036. View

Taylor S, Rosenzweig E, McDonald 3rd J, Sakiyama-Elbert S . Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. J Control Release. 2006; 113(3):226-35. PMC: 1615967. DOI: 10.1016/j.jconrel.2006.05.005. View

Fawcett J, Asher R . The glial scar and central nervous system repair. Brain Res Bull. 1999; 49(6):377-91. DOI: 10.1016/s0361-9230(99)00072-6. View

Willerth S, Faxel T, Gottlieb D, Sakiyama-Elbert S . The effects of soluble growth factors on embryonic stem cell differentiation inside of fibrin scaffolds. Stem Cells. 2007; 25(9):2235-44. PMC: 2637150. DOI: 10.1634/stemcells.2007-0111. View

Jain A, Kim Y, McKeon R, Bellamkonda R . In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. Biomaterials. 2005; 27(3):497-504. DOI: 10.1016/j.biomaterials.2005.07.008. View

Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead C, Fehlings M . Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci. 2006; 26(13):3377-89. PMC: 6673854. DOI: 10.1523/JNEUROSCI.4184-05.2006. View

Chow S, Moul J, TOBIAS C, Himes B, Liu Y, Obrocka M . Characterization and intraspinal grafting of EGF/bFGF-dependent neurospheres derived from embryonic rat spinal cord. Brain Res. 2000; 874(2):87-106. DOI: 10.1016/s0006-8993(00)02443-4. View

Rudge J, Silver J . Inhibition of neurite outgrowth on astroglial scars in vitro. J Neurosci. 1990; 10(11):3594-603. PMC: 6570102. View

Eriksson P, Perfilieva E, Bjork-Eriksson T, Alborn A, Nordborg C, Peterson D . Neurogenesis in the adult human hippocampus. Nat Med. 1998; 4(11):1313-7. DOI: 10.1038/3305. View

10.

Johnson P, Parker S, Sakiyama-Elbert S . Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury. J Biomed Mater Res A. 2009; 92(1):152-63. PMC: 2787862. DOI: 10.1002/jbm.a.32343. View

11.

Levenberg S, Burdick J, Kraehenbuehl T, Langer R . Neurotrophin-induced differentiation of human embryonic stem cells on three-dimensional polymeric scaffolds. Tissue Eng. 2005; 11(3-4):506-12. DOI: 10.1089/ten.2005.11.506. View

12.

Bain G, Kitchens D, Yao M, Huettner J, Gottlieb D . Embryonic stem cells express neuronal properties in vitro. Dev Biol. 1995; 168(2):342-57. DOI: 10.1006/dbio.1995.1085. View

13.

Courtine G, Song B, Roy R, Zhong H, Herrmann J, Ao Y . Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat Med. 2007; 14(1):69-74. PMC: 2916740. DOI: 10.1038/nm1682. View

14.

Sakiyama-Elbert S, Hubbell J . Development of fibrin derivatives for controlled release of heparin-binding growth factors. J Control Release. 2000; 65(3):389-402. DOI: 10.1016/s0168-3659(99)00221-7. View

15.

Cao Q, Howard R, Dennison J, Whittemore S . Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord. Exp Neurol. 2002; 177(2):349-59. DOI: 10.1006/exnr.2002.7981. View

16.

Furue M, Na J, Jackson J, Okamoto T, Jones M, Baker D . Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium. Proc Natl Acad Sci U S A. 2008; 105(36):13409-14. PMC: 2522264. DOI: 10.1073/pnas.0806136105. View

17.

Silva G, Czeisler C, Niece K, Beniash E, Harrington D, Kessler J . Selective differentiation of neural progenitor cells by high-epitope density nanofibers. Science. 2004; 303(5662):1352-5. DOI: 10.1126/science.1093783. View

18.

Bareyre F, Kerschensteiner M, Raineteau O, Mettenleiter T, Weinmann O, Schwab M . The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. Nat Neurosci. 2004; 7(3):269-77. DOI: 10.1038/nn1195. View

19.

Nakamura M, Okano H, Toyama Y, Dai H, Finn T, Bregman B . Transplantation of embryonic spinal cord-derived neurospheres support growth of supraspinal projections and functional recovery after spinal cord injury in the neonatal rat. J Neurosci Res. 2005; 81(4):457-68. DOI: 10.1002/jnr.20580. View

20.

Willerth S, Rader A, Sakiyama-Elbert S . The effect of controlled growth factor delivery on embryonic stem cell differentiation inside fibrin scaffolds. Stem Cell Res. 2009; 1(3):205-18. PMC: 2744946. DOI: 10.1016/j.scr.2008.05.006. View