Autoreactive T cells induce in vitro BM mesenchymal stem cell transdifferentiation to neural stem cells.
BACKGROUND
The degree of post-injury inflammation of the damaged area of a spinal cord is the main difference between the natural successful repair in inferior vertebrates and failure in superior vertebrates. The treatment of rats with anti-myelin lymphocytes after experimental spinal cord injury induces their functional recovery. On the other hand, mesenchymal stem cells (MSC) from adult BM implanted in injured areas recover the morphology and function of spinal cord in mammals. The purpose of this study was to determine whether there is a direct relationship between anti-nervous tissue T cells and MSC reparatory properties.


METHODS
Circulating autoreactive lymphocytes of patients with spinal cord injuries and amyotrophic lateral sclerosis were isolated and activated in vitro. These cells were cocultured with autologous MSC for 2-15 days. Cocultures of non-selected lymphocytes were used as controls.


RESULTS
After 48 h of coculture, MSC adopted a spindle shape with polarization of the cytoplasm that resembled bipolar neurons. Their nuclei diminished the nucleolus number and the chromatin lost its granular appearance. After 15 days of culture the cells developed the typical structure of a neural network. No morphologic changes were observed in control cultures. The differentiated cells reacted positively to tubuline III, GFAP and nestin. No differences were observed between the different patient cell sources.


CONCLUSIONS
We observed that autoreactive cells may induce the transdifferentiation of MSC to neural stem cells. This T-cell-MSC interaction may be a common phenomenon during physiologic nerve tissue repair.
Moviglia
G A
GA
Instituto Regina Mater, Paraguay 2452, Buenos Aires, 1121 ABL, Argentina. gmoviglia@reginamater.com
Varela
G
G
Gaeta
C A
CA
Brizuela
J A
JA
Bastos
F
F
Saslavsky
J
J
D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis; D015551:Autoimmunity / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D017252:CD3 Complex / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation / Q000379:methods; D048430:Cell Shape / Q000502:physiology; D018920:Coculture Techniques / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000737:chemistry / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry / Q000276:immunology; D064231:Nestin; D009474:Neurons / Q000737:chemistry / Q000166:cytology*; D011492:Protein Hydrolysates / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013119:Spinal Cord Injuries / Q000276:immunology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D014404:Tubulin / Q000032:analysis
D015703:Antigens, CD; D017252:CD3 Complex; D005904:Glial Fibrillary Acidic Protein; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D011492:Protein Hydrolysates; D015375:Receptors, Interleukin-2; D014404:Tubulin