Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations.
Bone marrow stromal cells (MSC) are non-hematopoietic support cells that can be easily derived from bone marrow aspirates. Human MSC are clinically attractive because they can be expanded to large numbers in culture and reintroduced into patients as autografts or allografts. We grafted human MSC derived from aspirates of four different donors into a subtotal cervical hemisection in adult female rats and found that cells integrated well into the injury site, with little migration away from the graft. Immunocytochemical analysis demonstrated robust axonal growth through the grafts of animals treated with MSC, suggesting that MSC support axonal growth after spinal cord injury (SCI). However, the amount of axon growth through the graft site varied considerably between groups of animals treated with different MSC lots, suggesting that efficacy may be donor-dependent. Similarly, a battery of behavioral tests showed partial recovery in some treatment groups but not others. Using ELISA, we found variations in secretion patterns of selected growth factors and cytokines between different MSC lots. In a dorsal root ganglion explant culture system, we tested efficacy of conditioned medium from three donors and found that average axon lengths increased for all groups compared to control. These results suggest that human MSC produce factors important for mediating axon outgrowth and recovery after SCI but that MSC lots from different donors vary considerably. To qualify MSC lots for future clinical application, such notable differences in donor or lot-lot efficacy highlight the need for establishing adequate characterization, including the development of relevant efficacy assays.
Neuhuber
Birgit
B
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Timothy Himes
B
B
Shumsky
Jed S
JS
Gallo
Gianluca
G
Fischer
Itzhak
I
D000293:Adolescent; D000328:Adult; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal; D016026:Bone Marrow Transplantation / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002642:Chick Embryo; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D011187:Posture / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D012684:Sensory Thresholds / Q000502:physiology; D013119:Spinal Cord Injuries / Q000601:surgery / Q000628:therapy*; D017154:Stromal Cells / Q000637:transplantation*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D017077:Culture Media, Conditioned; D016207:Cytokines; D019922:GAP-43 Protein; D016900:Neurofilament Proteins