Therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord

Hiromi Kumamaru, Hirokazu Saiwai, Kensuke Kubota, Kazu Kobayakawa, Kazuya Yokota, Yasuyuki Ohkawa, Keiichiro Shiba, Yukihide Iwamoto, Seiji Okada

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The transplantation of neural stem/precursor cells (NSPCs) is a promising therapeutic strategy for many neurodegenerative disorders including spinal cord injury (SCI) because it provides for neural replacement or trophic support. This strategy is now being extended to the treatment of chronic SCI patients. However, understanding of biological properties of chronically transplanted NSPCs and their surrounding environments is limited. Here, we performed temporal analysis of injured spinal cords and demonstrated their multiphasic cellular and molecular responses. In particular, chronically injured spinal cords were growth factorenriched environments, whereas acutely injured spinal cords were enriched by neurotrophic and inflammatory factors. To determine how these environmental differences affect engrafted cells, NSPCs transplanted into acutely, subacutely, and chronically injured spinal cords were selectively isolated by flow cytometry, and their whole transcriptomes were compared by RNA sequencing. This analysis revealed that NSPCs produced many regenerative/ neurotrophic molecules irrespective of transplantation timing, and these activities were prominent in chronically transplanted NSPCs. Furthermore, chronically injured spinal cords permitted engrafted NSPCs to differentiate into neurons/oligodendrocytes and provided more neurogenic environment for NSPCs than other environments. Despite these results demonstrate that transplanted NSPCs have adequate capacity in generating neurons/oligodendrocytes and producing therapeutic molecules in chronic SCI microenvironments, they did not improve locomotor function. Our results indicate that failure in chronic transplantation is not due to the lack of therapeutic activities of engrafted NSPCs but the refractory state of chronically injured spinal cords. Environmental modulation, rather modification of transplanting cells, will be significant for successful translation of stem cell-based therapies into chronic SCI patients.

Original languageEnglish
Pages (from-to)1535-1547
Number of pages13
JournalSTEM CELLS
Volume31
Issue number8
DOIs
Publication statusPublished - Aug 1 2013

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Neural Stem Cells
Spinal Cord
Spinal Cord Injuries
Transplantation
Oligodendroglia
Therapeutics
Stem Cells
RNA Sequence Analysis
Neurons
Nerve Growth Factors
Cell- and Tissue-Based Therapy
Transcriptome
Neurodegenerative Diseases
Flow Cytometry
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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Therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord. / Kumamaru, Hiromi; Saiwai, Hirokazu; Kubota, Kensuke; Kobayakawa, Kazu; Yokota, Kazuya; Ohkawa, Yasuyuki; Shiba, Keiichiro; Iwamoto, Yukihide; Okada, Seiji.

In: STEM CELLS, Vol. 31, No. 8, 01.08.2013, p. 1535-1547.

Research output: Contribution to journalArticle

Kumamaru, Hiromi ; Saiwai, Hirokazu ; Kubota, Kensuke ; Kobayakawa, Kazu ; Yokota, Kazuya ; Ohkawa, Yasuyuki ; Shiba, Keiichiro ; Iwamoto, Yukihide ; Okada, Seiji. / Therapeutic activities of engrafted neural stem/precursor cells are not dormant in the chronically injured spinal cord. In: STEM CELLS. 2013 ; Vol. 31, No. 8. pp. 1535-1547.
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