Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats
Abstract
Postinjury recovery in most tissues requires an effective dialog with macrophages; however, in the mammalian central nervous system, this dialog may be restricted (possibly due to its immune-privileged status), which probably contributes to its regeneration failure. We circumvented this by implanting macrophages, pre-exposed ex vivo to peripheral nerve segments, into transected rat spinal cord. This stimulated tissue repair and partial recovery of motor function, manifested behaviorally by movement of hind limbs, plantar placement of the paws and weight support, and electrophysiologically by cortically evoked hind-limb muscle response. We substantiated these findings immunohistochemically by demonstrating continuity of labeled nerve fibers across the transected site, and by tracing descending fibers distally to it by anterograde labeling. In recovered rats, retransection of the cord above the primary transection site led to loss of recovery, indicating the involvement of long descending spinal tracts. Injection of macrophages into the site of injury is relatively non-invasive and, as the cells are autologous, it may be developed into a clinical therapy.
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From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [135]
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- Authors
- Rapalino, O., Lazarov-Spiegler, O., Agranov, E., Velan, G. J., Yoles, E., Fraidakis, M., Soloman, A., Gepstein, R., Katz, A., Belkin, M., Hadani, M., & Schwartz, M.
- Affiliations
- Weizmann Institute of Science (IL)
- Meir Medical Center (IL)
- Karolinska Institutet (SE)
- Sheba Medical Center (IL)
- Venue
- Nature Medicine
- Published
- 1998-07
- Volume
- 4
- Issue
- 7
- Pages
- 814-821
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2039334993
- Cited by
- 788
- References
- 0
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 10 · 2018: 13 · 2017: 10 · 2016: 24 · 2015: 30 · 2014: 36 · 2013: 33 · 2012: 35
- FWCI
- 22.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- spinal cord transection, paraplegia, motor recovery, peripheral nerve stimulation, central nervous system regeneration, immune privilege, cell therapy
- MeSH terms
- Animals, Electrophysiology, Female, Follow-Up Studies, Macrophages, Male, Motor Activity, Paraplegia, Rats, Sprague-Dawley, Cell Transplantation, Rats
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