Lentiviral delivery of LMX1a enhances dopaminergic phenotype in differentiated human bone marrow mesenchymal stem cells.
Human mesenchymal stem cells (MSCs) reside in the bone marrow and are known for their ability to differentiate along the mesenchymal lineage (fat, bone, and cartilage). Recent works have suggested the possibility that these cells are also capable of differentiating toward the neuroectodermal lineage. Using lentiviral gene delivery, we sought to reprogram the bone marrow-derived MSCs toward dopaminergic differentiation through delivery of LMX1a, which was reported to be a key player in dopaminergic differentiation in both developmental animal models and embryonic stem cells. Transduction of cells with fluorescent reporter genes confirmed efficiency of gene delivery. On incubation of the LMX1a transduced cells in differentiation medium, the LMX1a protein was concentrated in the cells' nuclei and specific dopaminergic developmental genes were upregulated. Moreover, the transduced cells expressed higher levels of tyrosine hydroxylase, the rate limiting enzyme in dopamine synthesis, and secreted significantly higher level of dopamine in comparison to nontransduced cells. We hereby present a novel strategy to facilitate the dopaminergic differentiation of bone marrow-derived MSCs as a possible cell source for autologous transplantation for Parkinsonian patients in the future.
Barzilay
Ran
R
Department of Neurology, Laboratory of Neurosciences, Felsenstein Medical Research Center, Rabin Medical Center, Tel Aviv University, Sackler School of Medicine, Petah-Tikva, Israel.
Ben-Zur
Tali
T
Bulvik
Shlomo
S
Melamed
Eldad
E
Offen
Daniel
D
D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins; D016086:Lentivirus / Q000235:genetics* / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D008875:Middle Aged; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010300:Parkinson Disease / Q000628:therapy; D010641:Phenotype; D014157:Transcription Factors; D014161:Transduction, Genetic
D015415:Biomarkers; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C078021:LMX1A protein, human; D014157:Transcription Factors; D004298:Dopamine