MSC's in a Canine Disc Degeneration Model: May'08 J. Ortho Research

[Slackwater]

MSC = Mesenchymal Stem Stells
<span class="ev_code_GREEN">GFP</span> = Green Fluorescent Protein
PCR = Polymerase Chain Reaction
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There are two (2) references below with web links. <UL TYPE=SQUARE>First abstract has more text / explanation; it is longer with pictures (<span class="ev_code_RED">in color</span>).

Second abstract is shorter, same authors, looks like a pubmed.gov posting, a synopsis of ~11 pages in the Journal of Orthopaedic Research - May 2008, a much longer document and a lot of work.[/list]Please consider this as a "possible future treatment" for human use. There is a lot of heat, smoke, light, noise, ... about stem cells, much of it written by industry pundits, promoters, editors filling column space, ... The below includes data points that professional medical researchers can use to form a basis for more testing patterns to get reproducible results in animals before human trials in X years.


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#1
Orthopaedic Research Society, 54th Annual Meeting 2008
Abstract: 0440
Copyright © 2008 Orthopaedic Research Society

Basic Study on Cell Therapy for Disc Degeneration:
Investigation of Optimum Donor Cell Number in a Large Animal Model
Kenji Serigano, Daisuke Sakai, Akihiko Hiyama, Futoshi Tamura, Joji Mochida
Dept. of Orthopaedic Surgical Science and Center for Regenerative Medicine, Tokai University School of Medicine, Kanagawa, Japan

Degeneration was induced by nucleotomy (remove some of the nucleus). Stem cells were added at baseline, x10, and x100.

Group N: control, w/o operation
... increase # of stem cells, 10^5, 10^6, 10^7
Group D: operation, no stem cells

Fig. 1:
Disc Height x Stem Cell Number, and
MRI Pfirmann's Scale x Stem Cell #

Fig 2:
Macroscopic / Histologic evaluation



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#2
Journal of Orthopaedic Research
Volume 26, Issue 5 , Pages 589 - 600 (May 2008)
Copyright © 2008 Orthopaedic Research Society

Transplantation of mesenchymal stem cells in a canine disc degeneration model

Akihiko Hiyama 1 2, Joji Mochida 1 2, Toru Iwashina 1 2, Hiroko Omi 1 2, Takuya Watanabe 1 2, Kenji Serigano 1 2, Futoshi Tamura 1 2, Daisuke Sakai 1 2 *
1 Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, 259-1193, Japan
2 Center for Regenerative Medicine, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, 259-1193, Japan

Keywords
mesenchymal stem cells • intervertebral disc • disc degeneration • nucleus pulposus • regenerative medicine


Abstract
Transplantation of mesenchymal stem cells (MSCs) is effective in decelerating disc degeneration in small animals; much remains unknown about this new therapy in larger animals or humans.

Fas-ligand (FasL), which is only found in tissues with isolated immune privilege, is expressed in IVDs, particularly in the nucleus pulposus (NP). Maintaining the FasL level is important for IVD function. This study evaluated whether MSC transplantation has an effect on the suppression of disc degeneration and preservation of immune privilege in a canine model of disc degeneration.

Mature beagles were separated into a normal control group (NC), a MSC group, and the disc degeneration (nucleotomy-only) group. In the MSC group, 4 weeks after nucleotomy, MSCs were transplanted into the degeneration-induced discs. The animals were followed for 12 weeks after the initial operation. Subsequently, radiological, histological, biochemical, immunohistochemical, and RT-PCR analyses were performed.

MSC transplantation effectively led to the regeneration of degenerated discs. FACS and RT-PCR analyses of MSCs before transplantation demonstrated that the MSCs expressed FasL at the genetic level, not at the protein level. GFP-positive MSCs detected in the NP region 8 weeks after transplantation expressed FasL protein.

The results of this study suggest that MSC transplantation may contribute to the maintenance of IVD immune privilege by the differentiation of transplanted MSCs into cells expressing FasL.

© 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:589-600, 2008
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two-level lumbar surgical candidate