Skip to main content
SpringerLink
Log in

Transplantation of Heat-Shock Preconditioned Neural Stem/Progenitor Cells Combined with RGD-Functionalised Hydrogel Promotes Spinal Cord Functional Recovery in a Rat Hemi-Transection Model

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Background

Neural stem/progenitor cell (NSPC) transplantation in spinal cord injury (SCI) is a potential treatment that supports regeneration by promoting neuroprotection, remyelination, and neurite outgrowth. However, glial scarring hinders neuroregeneration and reduces the efficiency of cell transplantation. The present study aimed to enhance this neuroregeneration by surgically removing the glial scar and transplanting heat-shock (HS) preconditioned NSPCs in combination with Arg-Gly-Asp (RGD)-functionalised hydrogel in a rat spinal cord hemi-transection model.

Methods

Twelve Sprague-Dawley rats underwent spinal cord hemi-transection and were randomly divided into three treatment groups: hydrogel implantation (control group), NSPC-encapsulated hydrogel implantation, and HS-NSPC-encapsulated hydrogel implantation. HS preconditioning was applied to the NSPCs to reinforce cell retention and an RGD-functionalised hydrogel was used as a biomatrix.

Results

In vitro culture showed that preconditioned NSPCs highly differentiated into neurons and oligodendrocytes and exhibited higher proliferation and neurite outgrowth in hydrogels. Rats in the HS-NSPC-encapsulated hydrogel implantation group showed significantly improved functional recovery, neuronal and oligodendrocyte differentiation of transplanted cells, remyelination, and low fibrotic scar formation.

Conclusions

The surgical removal of the glial scar in combination with HS-preconditioning and RGD-functionalised hydrogels should be considered as a new paradigm in NSPC transplantation for spinal cord regeneration treatment.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

All data generated or analysed during this study are included in this published article.

Abbreviations

3D :

Three dimensional

BBB :

Basso, Beattie, Bresnahan Locomotor Rating Scale

BDNF :

Brain-derived neurotrophic factor

CNS :

Central nervous system

CXCR4 :

C-X-C chemokine receptor type 4

DAPI :

4,6-diamidino-2-phenylindole

FBS :

Fetal bovine serum

ECM :

Extracellular matrix

GAPHD :

Glyceraldehyde-3-phosphate dehydrogenase

GFAP :

Glial fibrillary acidic protein

HG :

Hydrogel

HS :

Heat-shock

HSP27 :

Heat-shock protein 70

HSP70 :

Heat-shock protein 70

LFB :

Luxol fast blue

MBP :

Myelin basic protein

NGF :

Nerve growth factor

NSPC :

Neural stem/progenitor cell

NSC :

Neural stem cells

OCT :

Optimal cutting temperature compound

PBS :

Phosphate-buffered saline

PFA :

Paraformaldehyde

PLO :

Poly-L-ornithine solution

RGD :

Arg-Gly-Asp

RT :

Room temperature

RT-PCR :

Real-time polymerase chain reaction

SCI :

Spinal cord injury

SOX2 :

Sex determining region Y-box 2

VEGF :

Vascular endothelial growth factor

References

  1. Bickenbach, J., Boldt, I., Brinkhof, M., Chamberlain, J., Cripps, R., & Fitzharris, M., et al. (2013). A global picture of spinal cord injury. In J. Bickenbach, C. Bodine, D. Brown, A. Burns, R. Campbell, & D. Cardenas (Eds.), International Perspectives on spinal cord Injury (pp. 11–42). World Health Organization.

  2. Hagen, E. M., Rekand, T., Gilhus, N. E., & Grønning, M. (2012). Traumatic spinal cord injuries–incidence, mechanisms and course. Tidsskrift for Den Norske Laegeforening, 132, 831–837.

    Article  PubMed  Google Scholar 

  3. Silva, N. A., Sousa, N., Reis, R. L., & Salgado, A. J. (2014). From basics to clinical: A comprehensive review on spinal cord injury. Progress in Neurobiology, 114, 25–57.

    Article  PubMed  Google Scholar 

  4. Gilbert, R. J., McKeon, R. J., Darr, A., Calabro, A., Hascall, V. C., & Bellamkonda, R. V. (2005). CS-4, 6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension. Molecular and Cellular Neuroscience, 29, 45–558.

    Article  Google Scholar 

  5. Fawcett, J. W. (2006). Overcoming inhibition in the damaged spinal cord. Journal of Neurotrauma, 23, 371–383.

    Article  PubMed  Google Scholar 

  6. Huang, L., Fu, C., Xiong, F., He, C., & Wei, Q. (2021). Stem cell therapy for spinal cord injury. Cell Transplantation, 30, 096368972198926. 

  7. Weiss, S., Dunne, C., Hewson, J., Wohl, C., Wheatley, M., Peterson, A. C., Weiss, S., Dunne, C., Hewson, J., Wohl, C., Wheatley, M., Peterson, A. C., & Reynolds, B. A. (1996). Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. Journal of Neuroscience, 16, 7599–7609.

    Article  CAS  PubMed  Google Scholar 

  8. Yang, J., Jiang, Z., Fitzgerald, D. C., Ma, C., Yu, S., Li, H., Yang, J., Jiang, Z., Fitzgerald, D. C., Ma, C., Yu, S., Li, H., Zhao, Z., Li, Y., Ciric, B., Curtis, M., Rostami, A., & Zhang, G.-X. (2009). Adult neural stem cells expressing IL-10 confer potent immunomodulation and remyelination in experimental autoimmune encephalitis. The Journal of Clinical Investigation, 119(12), 3678–3691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Zhu, Y., Uezono, N., Yasui, T., & Nakashima, K. (2018). Neural stem cell therapy aiming at better functional recovery after spinal cord injury. Developmental Dynamics, 247(1), 75–84.

    Article  PubMed  Google Scholar 

  10. Assunção-Silva, R. C., Gomes, E. D., Sousa, N., Silva, N. A., & Salgado, A. J. (2015). Hydrogels and cell based therapies in spinal cord injury regeneration. Stem Cells International, 2015, 1–24. 

  11. Austin, J. W., Kang, C. E., Baumann, M. D., DiDiodato, L., Satkunendrarajah, K., Wilson, J. R., et al. (2012). The effects of intrathecal injection of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis. Biomaterials, 33, 4555–4564.

    Article  CAS  PubMed  Google Scholar 

  12. Li, G., Che, M. T., Zhang, K., Qin, L. N., Zhang, Y. T., Chen, R. Q., Li, Ge., Che, M.-T., Zhang, Ke., Qin, L.-N., Zhang, Y.-T., Chen, R.-Q., Rong, L.-M., Liu, S., Ding, Y., Shen, H.-Y., Long, S.-M., Wu, J.-L., Ling, E.-A., & Zeng, Y.-S. (2016). Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury. Biomaterials, 83, 233–248.

    Article  CAS  PubMed  Google Scholar 

  13. Dutta, R. C., & Dutta, A. K. (2009). Cell-interactive 3D-scaffold; advances and applications. Biotechnology Advances, 27, 334–339.

    Article  CAS  PubMed  Google Scholar 

  14. Chan, G., & Mooney, D. J. (2008). New materials for tissue engineering: Towards greater control over the biological response. Trends in Biotechnology, 26, 382–392.

    Article  CAS  PubMed  Google Scholar 

  15. Straley, K. S., Foo, C. W. P., & Heilshorn, S. C. (2010). Biomaterial design strategies for the treatment of spinal cord injuries. Journal of Neurotrauma, 27, 1–19.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wang, L. S., Chung, J. E., Chan, P. P., & Kurisawa, M. (2010). Injectable biodegradable hydrogels with tunable mechanical properties for the stimulation of neurogenesic differentiation of human mesenchymal stem cells in 3D culture. Biomaterials, 31, 1148–1157.

    Article  PubMed  Google Scholar 

  17. Tam, R. Y., Cooke, M. J., & Shoichet, M. S. (2012). A covalently modified hydrogel blend of hyaluronan–methyl cellulose with peptides and growth factors influences neural stem/progenitor cell fate. Journal of Materials Chemistry, 22, 19402–19411.

    Article  CAS  Google Scholar 

  18. Sakata, H., Niizuma, K., Wakai, T., Narasimhan, P., Maier, C. M., & Chan, P. H. (2012). Neural stem cells genetically modified to overexpress cu/zn-superoxide dismutase enhance amelioration of ischemic stroke in mice. Stroke, 43, 2423–2429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lan, F., Liu, J., Narsinh, K. H., Hu, S., Han, L., Lee, A. S., et al. (2012). Safe genetic modification of cardiac stem cells using a site-specific integration technique. Circulation, 126, S20–S28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Morange, M. (2005). What history tells us II. The discovery of chaperone function. Journal of Biosciences, 30, 461–464.

    Article  CAS  PubMed  Google Scholar 

  21. Robinson, M. B., Tidwell, J. L., Gould, T., Taylor, A. R., Newbern, J. M., Graves, J., Robinson, M. B., Tidwell, J. L., Gould, T., Taylor, A. R., Newbern, J. M., Graves, J., Tytell, M., & Milligan, C. E. (2005). Extracellular heat shock protein 70: A critical component for motoneuron survival. Journal of Neuroscience, 25, 9735–9745.

    Article  CAS  PubMed  Google Scholar 

  22. Chen, Y., Voegeli, T. S., Liu, P. P., Noble, E. G., & Currie, R. W. (2007). Heat shock paradox and a new role of heat shock proteins and their receptors as anti-inflammation targets. Inflammation & Allergy: Drug Targets, 6, 91–100.

    Article  CAS  PubMed  Google Scholar 

  23. Zhou, Y., Xu, L., Song, X., Ding, L., Chen, J., Wang, C., Zhou, Y., Xu, L., Song, X., Ding, L., Chen, J., Wang, C., Gan, Y., Zhu, X., Yu, Y., & Liang, Q. (2014). The potential role of heat shock proteins in acute spinal cord injury. European Spine Journal, 23, 1480–1490.

    Article  PubMed  Google Scholar 

  24. Kim, W. K., Kim, W. H., Kweon, O. K., & Kang, B. J. (2022). Heat-shock proteins can potentiate the therapeutic ability of Cryopreserved Mesenchymal Stem cells for the treatment of Acute spinal cord Injury in Dogs. Stem Cell Reviews and Report, 18, 1461–1477.

    Article  CAS  Google Scholar 

  25. Dasari, V. R., Veeravalli, K. K., & Dinh, D. H. (2014). Mesenchymal stem cells in the treatment of spinal cord injuries: A review. World Journal of Stem Cells, 6(2), 120.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pekny, M., & Nilsson, M. (2005). Astrocyte activation and reactive gliosis. Glia, 50(4), 427–434.

    Article  PubMed  Google Scholar 

  27. Shaik, S., Hayes, D., Gimble, J., & Devireddy, R. (2017). Inducing heat shock proteins enhances the stemness of frozen–thawed adipose tissue-derived stem cells. Stem Cells and Development, 26, 608–616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Livak, K. J., & Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2 – ∆∆CT method. Methods, 25, 402–408.

    Article  CAS  PubMed  Google Scholar 

  29. Faul, F., Erdfelder, E., Buchner, A., & Lang, A. G. (2009). Statistical power analyses using G* power 3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41(4), 1149–1160.

    Article  PubMed  Google Scholar 

  30. Abbaszadeh, H. A., Niknazar, S., Darabi, S., Roozbahany, N. A., Noori-Zadeh, A., Ghoreishi, S. K., Abbaszadeh, H.-A., Niknazar, S., Darabi, S., Ahmady Roozbahany, N., Noori-Zadeh, A., Ghoreishi, S. K., Khoramgah, M. S., & Sadeghi, Y. (2018). Stem cell transplantation and functional recovery after spinal cord injury: A systematic review and meta-analysis. Anatomy and Cell Biology, 51(3), 180–188.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lin, X. J., Wen, S., Deng, L. X., Dai, H., Du, X., Chen, C., et al. (2020). Spinal cord lateral hemisection and asymmetric behavioral assessments in adult rats. Journal of Visualized Experiments: Jove, 157, e57126.

  32. Chen, Z. L., Yu, W. M., & Strickland, S. (2007). Peripheral regeneration. Annual Review of Neuroscience, 30, 209–233.

    Article  PubMed  Google Scholar 

  33. Battersby, A., Jones, R. D., Lilley, K. S., McFarlane, R. J., Braig, H. R., Allen, N. D., Battersby, A., Jones, R. D., Lilley, K. S., McFarlane, R. J., Braig, H. R., Allen, N. D., & Wakeman, J. A. (2007). Comparative proteomic analysis reveals differential expression of Hsp25 following the directed differentiation of mouse embryonic stem cells. Biochimica Et Biophysica Acta, 1773, 147–156.

    Article  CAS  PubMed  Google Scholar 

  34. Chen, J., Crawford, R., Chen, C., & Xiao, Y. (2013). The key regulatory roles of the PI3K/Akt signaling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration. Tissue Engineering. Part B, Reviews, 19(6), 516–528.

    Article  CAS  PubMed  Google Scholar 

  35. Gao, F., Hu, X. Y., Xie, X. J., Xu, Q. Y., Wang, Y. P., Liu, X. B., Gao, F., Hu, X.-Y., Xie, X.-J., Xu, Q.-Y., Wang, Y.-P., Liu, X.-B., Xiang, M.-X., Sun, Y., & Wang, J.-a. (2010). Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways. Journal of Zhejiang University. Science. B, 11, 608–617.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Friedman, W. J., Thakur, S., Seidman, L., & Rabson, A. B. (1996). Regulation of nerve growth factor mRNA by interleukin-1 in rat hippocampal astrocytes is mediated by NFκB. Journal of Biological Chemistry, 271, 31115–31120.

    Article  CAS  PubMed  Google Scholar 

  37. Lipsky, R. H., Xu, K., Zhu, D., Kelly, C., Terhakopian, A., Novelli, A., et al. (2001). Nuclear factor κB is a critical determinant in N-methyl‐d‐aspartate receptor‐mediated neuroprotection. Journal of Neurochemistry, 78, 254–264.

    Article  CAS  PubMed  Google Scholar 

  38. Sart, S., Tsai, A. C., Li, Y., & Ma, T. (2014). Three-dimensional aggregates of mesenchymal stem cells: Cellular mechanisms, biological properties, and applications. Tissue Engineering. Part B, Reviews, 20, 365–380.

    Article  PubMed  Google Scholar 

  39. Ye, Z., Zhou, Y., Cai, H., & Tan, W. (2011). Myocardial regeneration: Roles of stem cells and hydrogels. Advanced Drug Delivery Reviews, 63, 688–697.

    Article  CAS  PubMed  Google Scholar 

  40. Baharvand, H., Fathi, A., van Hoof, D., & Salekdeh, G. H. (2007). Concise review: Trends in stem cell proteomics. Stem Cells, 25, 1888–1903.

    Article  CAS  PubMed  Google Scholar 

  41. Read, D. E., & Gorman, A. M. (2009). Heat shock protein 27 in neuronal survival and neurite outgrowth. Biochemical and Biophysical Research Communications, 382, 6–8.

    Article  CAS  PubMed  Google Scholar 

  42. Lu, P., Wang, Y., Graham, L., McHale, K., Gao, M., Wu, D., Lu, P., Wang, Y., Graham, L., McHale, K., Gao, M., Wu, Di., Brock, J., Blesch, A., Rosenzweig, E., Havton, L., Zheng, B., Conner, J., Marsala, M., & Tuszynski, M. (2012). Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell, 150, 1264–1273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ek, C. J., Habgood, M. D., Callaway, J. K., Dennis, R., Dziegielewska, K. M., Johansson, P. A., et al. (2010). Spatio-temporal progression of grey and white matter damage following contusion injury in rat spinal cord. PLoS One, 5(8), e12021.

  44. Peng, H., Kolb, R., Kennedy, J. E., & Zheng, J. (2007). Differential expression of CXCL12 and CXCR4 during human fetal neural progenitor cell differentiation. Journal of Neuroimmune Pharmacology: The Official Journal of the Society on Neuroimmune Pharmacology, 2, 251–258.

    Article  PubMed  Google Scholar 

  45. Orr, M. B., & Gensel, J. C. (2018). Spinal cord injury scarring and inflammation: Therapies targeting glial and inflammatory responses. Neurotherapeutics, 15, 541–553.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Amor, S., & Woodroofe, M. N. (2014). Innate and adaptive immune responses in neurodegeneration and repair. Immunology, 141, 287–291.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Chen, L. W., Kuang, F., Wei, L. C., Ding, Y. X., Yung, K. K., & Chan, Y. S. (2011). Potential application of induced pluripotent stem cells in cell replacement therapy for Parkinson’s disease. CNS & Neurological Disorders: Drug Targets, 10, 449–458.

    Article  CAS  Google Scholar 

  48. Tsuji, O., Miura, K., Okada, Y., Fujiyoshi, K., Mukaino, M., Nagoshi, N., Tsuji, O., Miura, K., Okada, Y., Fujiyoshi, K., Mukaino, M., Nagoshi, N., Kitamura, K., Kumagai, G., Nishino, M., Tomisato, S., Higashi, H., Nagai, T., Katoh, H., … Okano, H. (2010). Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proceedings National Academy of Sciences U S A, 107, 12704–12709.

    Article  CAS  Google Scholar 

  49. Willis, C. M., Nicaise, A. M., Peruzzotti-Jametti, L., & Pluchino, S. (2020). The neural stem cell secretome and its role in brain repair. Brain Research, 1729, 146615.

    Article  PubMed  Google Scholar 

  50. Campisi, J., & Fleshner, M. (2003). Role of extracellular HSP72 in acute stress-induced potentiation of innate immunity in active rats. Journal of Applied Physiology, 94, 43–52.

    Article  CAS  PubMed  Google Scholar 

  51. Neumann, H. (2000). The immunological microenvironment in the CNS: Implications on neuronal cell death and survival. Journal of Neural Transmission. Supplementum, 59, 59–68.

    CAS  PubMed  Google Scholar 

  52. Kim, H., Cooke, M. J., & Shoichet, M. S. (2012). Creating permissive microenvironments for stem cell transplantation into the central nervous system. Trends in Biotechnology, 30, 55–63.

    Article  CAS  PubMed  Google Scholar 

  53. Nicaise, A. M., D’Angelo, A., Ionescu, R. B., Krzak, G., Willis, C. M., & Pluchino, S. (2022). The role of neural stem cells in regulating glial scar formation and repair. Cell and Tissue Research, 387, 399–414.

    Article  PubMed  Google Scholar 

  54. Tseng, T. C., Tao, L., Hsieh, F. Y., Wei, Y., Chiu, I. M., & Hsu, S. H. (2015). An injectable, self-healing hydrogel to repair the central nervous system. Advanced Materials, 27, 3518–3524.

    Article  CAS  PubMed  Google Scholar 

  55. Banerjee, A., Arha, M., Choudhary, S., Ashton, R. S., Bhatia, S. R., Schaffer, D. V., Banerjee, A., Arha, M., Choudhary, S., Ashton, R. S., Bhatia, S. R., Schaffer, D. V., & Kane, R. S. (2009). The influence of hydrogel modulus on the proliferation and differentiation of encapsulated neural stem cells. Biomaterials, 30, 4695–4699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Haruna, N., & Huang, J. (2020). Investigating the dynamic Biophysical Properties of a tunable hydrogel for 3D cell culture. Journal of Cytology Tissue Biology, 7, 030.

    Google Scholar 

  57. Tajiri, N., Kaneko, Y., Shinozuka, K., Ishikawa, H., Yankee, E., McGrogan, M., Tajiri, N., Kaneko, Y., Shinozuka, K., Ishikawa, H., Yankee, E., McGrogan, M., Case, C., & Borlongan, C. V. (2013). Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site. PLoS One, 8, e74857. 

  58. Poplawski, G. H. D., Kawaguchi, R., Van Niekerk, E., Lu, P., Mehta, N., Canete, P., Poplawski, G. H. D., Kawaguchi, R., Van Niekerk, E., Lu, P., Mehta, N., Canete, P., Lie, R., Dragatsis, I., Meves, J. M., Zheng, B., Coppola, G., & Tuszynski, M. H. (2020). Injured adult neurons regress to an embryonic transcriptional growth state. Nature, 581, 77–82.

    Article  CAS  PubMed  Google Scholar 

  59. Han, Q., Xie, Y., Ordaz, J. D., Huh, A. J., Huang, N., Wu, W., et al. (2020). Restoring cellular energetics promotes axonal regeneration and functional recovery after spinal cord injury. Cell Metabolism, 31, 623–41e8.

  60. Marín, O., Valiente, M., Ge, X., & Tsai, L. H. (2010). Guiding neuronal cell migrations. Cold Spring Harbor Perspectives in Biology, 2, a001834.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Moraga, A., Pradillo, J. M., Cuartero, M. I., Hernández-Jiménez, M., Oses, M., Moro, M. A., et al. (2014). Toll-like receptor 4 modulates cell migration and cortical neurogenesis after focal cerebral ischemia. The Faseb Journal, 28, 4710–4718.

    Article  CAS  PubMed  Google Scholar 

  62. DeGeer, J., Kaplan, A., Mattar, P., Morabito, M., Stochaj, U., Kennedy, T. E., DeGeer, J., Kaplan, A., Mattar, P., Morabito, M., Stochaj, U., Kennedy, T. E., Debant, A., Cayouette, M., Fournier, A. E., & Lamarche-Vane, N. (2015). Hsc70 chaperone activity underlies Trio GEF function in axon growth and guidance induced by netrin-1. Journal of Cell Biology, 210, 817–832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank all the members who contributed to this article.

Funding

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (No. 2018R1D1A1B07047451). The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

Author information

Authors and Affiliations

  1. Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, Korea

    Woo Keyoung Kim & Byung-Jae Kang

  2. BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul, 08826, Korea

    Woo Keyoung Kim & Byung-Jae Kang

Authors
  1. Woo Keyoung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Byung-Jae Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WKK was involved in study design and performed experiments, data analysis, and manuscript writing. BJK were involved in study design and revised the manuscript. All authors read and approved the manuscript.

Corresponding author

Correspondence to Byung-Jae Kang.

Ethics declarations

Ethics Approval and Consent to Participate

The study was approved by the Animal Care and Use Committee of Seoul National University (SNU-220103-6-1; Title: Development of spinal cord injury treatment using neural stem/progenitor cells; Date of approval: April 13, 2022).

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, W.K., Kang, BJ. Transplantation of Heat-Shock Preconditioned Neural Stem/Progenitor Cells Combined with RGD-Functionalised Hydrogel Promotes Spinal Cord Functional Recovery in a Rat Hemi-Transection Model. Stem Cell Rev and Rep 20, 283–300 (2024). https://doi.org/10.1007/s12015-023-10637-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-023-10637-8

Keywords

Search

Navigation