Cell therapy for spinal cord repair: optimization of biologic scaffolds for survival and neural differentiation of human bone marrow stromal cells.
OBJECTIVE
The suppression of cell apoptosis using a biodegradable scaffold to replace the missing or altered extracellular matrix (ECM) could increase the survival of transplanted cells and thus increase the effectiveness of cell therapy.


METHODS
We studied the best conditions for the proliferation and differentiation of human bone marrow stromal cells (hBMSC) when cultured on different biologic scaffolds derived from fibrin and blood plasma, and analyzed the best concentrations of fibrinogen, thrombin and calcium chloride for favoring cell survival. The induction of neural differentiation of hBMSC was done by adding to these scaffolds different growth factors, such as nerve growth factor (NGF), brain-derived-neurotrophic factor (BDNF) and retinoic acid (RA), at concentrations of 100 ng/mL (NGF and BDNF) and 1 micro/mL (RA), over 7 days.


RESULTS
Although both types of scaffold allowed survival and neural differentiation of hBMSC, the results showed a clear superiority of platelet-rich plasma (PRP) scaffolds, mainly after BDNF administration, allowing most of the hBMSC to survive and differentiate into a neural phenotype.


CONCLUSIONS
Given that clinical trials for spinal cord injury using hBMSC are starting, these findings may have important clinical applications.
Zurita
Mercedes
M
Neuroscience Research Unit of Surgical Research Service, Hospital Puerta de Hierro-Majadahonda, Madrid, Spain.
Otero
Laura
L
Aguayo
Concepción
C
Bonilla
Celia
C
Ferreira
Edgar
E
Parajón
Avelino
A
Vaquero
Jesús
J
D001672:Biocompatible Materials / Q000737:chemistry* / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005337:Fibrin / Q000737:chemistry; D006801:Humans; D020287:In Situ Nick-End Labeling; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D053657:Platelet-Rich Plasma / Q000737:chemistry; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D054457:Tissue Scaffolds / Q000737:chemistry* / Q000706:statistics & numerical data; D014212:Tretinoin / Q000494:pharmacology
D001672:Biocompatible Materials; D019208:Brain-Derived Neurotrophic Factor; D014212:Tretinoin; D005337:Fibrin; D020932:Nerve Growth Factor