Noggin induces human bone marrow-derived mesenchymal stem cells to differentiate into neural and photoreceptor cells.
The present study was undertaken to explore the effect of noggin on neuronal differentiating potential of human bone marrow-derived mesenchymal stem cells (hBMMSCs) in vitro so as to provide a means of alleviate retinal degeneration. A green fluorescent protein-tagged noggin gene was transferred into adult hBMMSCs or induce hBMMSCs with classical inducer, epidermal growth factor(EGF). Neurons were observed as early as 48 h after transduction of hBMMSCs with a noggin adenoviral vector. Differentiation peaked by 10 days in culture, and these differentiated cells expressed multiple markers including rhodopsin (18.4 +/- 1.5% of cells), chx10 (4.8 +/- 0.6%), nestin (4.2 +/- 0.8%), and Nrl (3.7 +/- 0.4%), as verified by immunofluorescence staining. Noggin-transduced cells produced more photoreceptor cells than non-transduced cells, suggesting that noggin has the ability to induce hBMMSCs to trans-differentiate into photoreceptor cells. In contrast, induction with EGF for 10 days led to lower levels of rhodopsin and chx10, and undetectable levels of Nrl and Nestin. These findings suggested noggin-transduced hBMMSCs produced more photoreceptor cells than EGF-induced cells. It is suggested that the present protocol has application in cell replacement therapy for patients suffering from photoreceptor cell loss.
Tao
Yu X
YX
Southwest Hospital/ Southwest Eye Hospital, Chongqing Institute of Retina, Third Military Medical University, Chongqing 400038, PR China
Xu
Hai W
HW
Zheng Q
Yin
Y
FitzGibbon
Thomas
T
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D054338:Cell Transdifferentiation; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D009474:Neurons / Q000166:cytology*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology; D014161:Transduction, Genetic; D000099176:Noggin Protein
D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; D000099176:Noggin Protein