Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

Tissue damage induces cells into reprogramming-like cellular state, which contributes to tissue regeneration. However, whether factors promoting the cell reprogramming favor tissue regeneration remains elusive. Here we identified combination of small chemical compounds including drug cocktails robustly promoting in vitro cell reprogramming. We then administrated the drug cocktails to mice with acute liver injuries induced by partial hepatectomy or toxic treatment. Our results demonstrated that the drug cocktails which promoted cell reprogramming in vitro improved liver regeneration and hepatic function in vivo after acute injuries. The underlying mechanism could be that expression of pluripotent genes activated after injury is further upregulated by drug cocktails. Thus our study offers proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose.
Animals ; Cellular Reprogramming ; drug effects ; Cellular Reprogramming Techniques ; methods ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Mice

Human embryonic stem cells (hESCs) are pluripotent cells that have the ability of unlimited self-renewal and can be differentiated into different cell lineages, including neural stem (NS) cells. Diverse regulatory signaling pathways of neural stem cells differentiation have been discovered, and this will be of great benefit to uncover the mechanisms of neuronal differentiation in vivo and in vitro. However, the limitations of hESCs resource along with the religious and ethical concerns impede the progress of ESCs application. Therefore, the induced pluripotent stem cells (iPSCs) via somatic cell reprogramming have opened up another new territory for regenerative medicine. iPSCs now can be derived from a number of lineages of cells, and are able to differentiate into certain cell types, including neurons. Patient-specifi c iPSCs are being used in human neurodegenerative disease modeling and drug screening. Furthermore, with the development of somatic direct reprogramming or lineage reprogramming technique, a more effective approach for regenerative medicine could become a complement for iPSCs.
Cell Differentiation ; Cell Lineage ; Cell Transdifferentiation ; Cellular Reprogramming ; drug effects ; Embryonic Stem Cells ; cytology ; Humans ; Induced Pluripotent Stem Cells ; cytology ; transplantation ; Neural Stem Cells ; cytology ; transplantation ; Neurodegenerative Diseases ; therapy ; Regenerative Medicine ; Transcription Factors ; genetics ; metabolism

Ascorbic Acid ; chemistry ; pharmacology ; Cellular Reprogramming ; Genetic Vectors ; genetics ; metabolism ; Histone Deacetylases ; genetics ; metabolism ; Humans ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; Protein Kinase Inhibitors ; chemistry ; pharmacology ; RNA, Small Interfering ; metabolism

Embryonic stem cell is promising for regenerative medicine. However, its application is hampered by the utilization of eggs in most established methods. Recently, a new pluripotent stem cell establishing method was reported that, mouse and human differentiated cells could be induced reprogrammed into a pluripotent state by expressing exogenetic stem factors such as Oct4, Sox2, et al, through retroviral transduction. This approach avoiding egg use is a great breakthrough not only in stem cell technology but also present theory hypothesis of reprogramming. Here these works were reviewed in this article. Both the mechanism of induced reprogramming and the prospects of induced pluripotent stem cells were discussed.
Animals ; Cell Differentiation ; genetics ; Cells, Cultured ; Cellular Reprogramming ; drug effects ; genetics ; Humans ; Octamer Transcription Factor-3 ; metabolism ; Pluripotent Stem Cells ; cytology ; Retroviridae ; genetics ; SOXB1 Transcription Factors ; metabolism ; Transduction, Genetic

To establish a co-culture system of nuclear transferred embryos in bovine, effects of co-culture cell types, passages and cryopreservation as well as addition of BFF or FBS were investigated. The results showed that embryos co-cultured with oviductal epithelial cell and granulosa cell achieved significantly higher blastocyst rate compared with the control group (P < 0.05) and co-cultured with oviductal epithelial cell had more embryo cell number than those with granulosa cell. Passages of co-culture cells significantly affected the blastocyst rate and embryo cell number (P < 0.05), and cryopreservation decreased the blastocyst rate and embryo cell number remarkably. Supplemention of BFF increased blastocyste rate significantly (P < 0.05). In conclusion, co-cultured with fresh primary oviductal epithelial cell along with addition of 10% BFF in SOFaa could improve development of nuclear transferred bovine embryo in vitro.
Animals ; Cattle ; Cellular Reprogramming ; Cloning, Organism ; methods ; Coculture Techniques ; Culture Media ; Embryo, Mammalian ; cytology ; drug effects ; Embryonic Development ; Epithelial Cells ; cytology ; drug effects ; Fallopian Tubes ; cytology ; Female ; Granulosa Cells ; cytology ; drug effects ; Nuclear Transfer Techniques