Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats

Laboratory investigation

Rishi N. Sheth, Glen Manzano, Xiuming Li, Allan D Levi

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Object. Human bone marrow stromal cells (hMSCs) constitute a potential source of pluripotent stem cells. In the present study, hMSCs were transplanted into an area of spinal cord contusion in nude rats to determine their survival, differentiation, potential for neuroprotection, and influence on axonal growth and functional recovery. Methods. Twenty-nine animals received 6 × 10 5 hMSCs in 6 μl medium 1 week after a contusion, while 14 control animals received an injection of 6 μl medium alone. Basso-Beattie-Bresnahan (BBB) tests were performed weekly. The spinal cords were collected at 6 weeks posttransplantation for histological analysis and assessment of tissue injury. Results. Immunostaining with anti-human mitochondria antibody and pretransplantation labeling with green fluorescent protein demonstrated that the grafted hMSCs survived and were capable of achieving a flattened appearance in the grafted area; however, none of the transplanted cells stained positively for human-specific neuronal, anti-neurofilament H or glial fibrillary acidic protein within the sites of engraftment. While neuronal or astrocytic differentiation was not seen, cells lining blood vessels in the vicinity of the transplant stained positively for anti-human endothelium CD105 antibody. Staining for anti-neurofilament H antibody demonstrated abundant axonlike structures around the transplanted area in the hMSC group. Tissue sparing analysis showed that animals with grafted hMSCs had a smaller area of contusion cyst compared with controls, but there was no significant difference between the two groups in BBB scores. Conclusions. The grafted hMSCs survived for ≥ 6 weeks posttransplantation, although they did not differentiate into neural or glial cells. Cells with human endothelial characteristics were observed. Spinal cord-injured rats grafted with hMSCs had smaller contusion cavities, which did not have a significant influence on functional recovery.

Original languageEnglish
Pages (from-to)153-162
Number of pages10
JournalJournal of Neurosurgery: Spine
Volume8
Issue number2
DOIs
StatePublished - Feb 1 2008

Fingerprint

Nude Rats
Contusions
Mesenchymal Stromal Cells
Spinal Cord
Transplantation
Intermediate Filaments
Antibodies
Pluripotent Stem Cells
Glial Fibrillary Acidic Protein
Green Fluorescent Proteins
Spinal Cord Injuries
Neuroglia
Endothelium
Blood Vessels
Cysts

Keywords

  • Bone marrow stromal cells
  • Differentiation
  • Neuroprotection
  • Rat
  • Spinal cord injury
  • Transplantation

ASJC Scopus subject areas

  • Clinical Neurology
  • Surgery
  • Neurology

Cite this

Transplantation of human bone marrow-derived stromal cells into the contused spinal cord of nude rats : Laboratory investigation. / Sheth, Rishi N.; Manzano, Glen; Li, Xiuming; Levi, Allan D.

In: Journal of Neurosurgery: Spine, Vol. 8, No. 2, 01.02.2008, p. 153-162.

Research output: Contribution to journalArticle

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N2 - Object. Human bone marrow stromal cells (hMSCs) constitute a potential source of pluripotent stem cells. In the present study, hMSCs were transplanted into an area of spinal cord contusion in nude rats to determine their survival, differentiation, potential for neuroprotection, and influence on axonal growth and functional recovery. Methods. Twenty-nine animals received 6 × 10 5 hMSCs in 6 μl medium 1 week after a contusion, while 14 control animals received an injection of 6 μl medium alone. Basso-Beattie-Bresnahan (BBB) tests were performed weekly. The spinal cords were collected at 6 weeks posttransplantation for histological analysis and assessment of tissue injury. Results. Immunostaining with anti-human mitochondria antibody and pretransplantation labeling with green fluorescent protein demonstrated that the grafted hMSCs survived and were capable of achieving a flattened appearance in the grafted area; however, none of the transplanted cells stained positively for human-specific neuronal, anti-neurofilament H or glial fibrillary acidic protein within the sites of engraftment. While neuronal or astrocytic differentiation was not seen, cells lining blood vessels in the vicinity of the transplant stained positively for anti-human endothelium CD105 antibody. Staining for anti-neurofilament H antibody demonstrated abundant axonlike structures around the transplanted area in the hMSC group. Tissue sparing analysis showed that animals with grafted hMSCs had a smaller area of contusion cyst compared with controls, but there was no significant difference between the two groups in BBB scores. Conclusions. The grafted hMSCs survived for ≥ 6 weeks posttransplantation, although they did not differentiate into neural or glial cells. Cells with human endothelial characteristics were observed. Spinal cord-injured rats grafted with hMSCs had smaller contusion cavities, which did not have a significant influence on functional recovery.

AB - Object. Human bone marrow stromal cells (hMSCs) constitute a potential source of pluripotent stem cells. In the present study, hMSCs were transplanted into an area of spinal cord contusion in nude rats to determine their survival, differentiation, potential for neuroprotection, and influence on axonal growth and functional recovery. Methods. Twenty-nine animals received 6 × 10 5 hMSCs in 6 μl medium 1 week after a contusion, while 14 control animals received an injection of 6 μl medium alone. Basso-Beattie-Bresnahan (BBB) tests were performed weekly. The spinal cords were collected at 6 weeks posttransplantation for histological analysis and assessment of tissue injury. Results. Immunostaining with anti-human mitochondria antibody and pretransplantation labeling with green fluorescent protein demonstrated that the grafted hMSCs survived and were capable of achieving a flattened appearance in the grafted area; however, none of the transplanted cells stained positively for human-specific neuronal, anti-neurofilament H or glial fibrillary acidic protein within the sites of engraftment. While neuronal or astrocytic differentiation was not seen, cells lining blood vessels in the vicinity of the transplant stained positively for anti-human endothelium CD105 antibody. Staining for anti-neurofilament H antibody demonstrated abundant axonlike structures around the transplanted area in the hMSC group. Tissue sparing analysis showed that animals with grafted hMSCs had a smaller area of contusion cyst compared with controls, but there was no significant difference between the two groups in BBB scores. Conclusions. The grafted hMSCs survived for ≥ 6 weeks posttransplantation, although they did not differentiate into neural or glial cells. Cells with human endothelial characteristics were observed. Spinal cord-injured rats grafted with hMSCs had smaller contusion cavities, which did not have a significant influence on functional recovery.

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