Mesenchymal Stem Cells Stimulate Endogenous Neurogenesis in the Subventricular Zone of Adult Mice

Kan, Inna; Barhum, Yael; Melamed, Eldad; Offen, Daniel

doi:10.1007/s12015-010-9190-x

Cited by 72 publications

(57 citation statements)

References 54 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well accepted that SVZ-derived neuroblasts migrate in their immature form and differentiate only after the migratory period, and hence do not differentiate within the SVZ [76]. Nevertheless, we are not the first to observe this phenomenon, and BrdU +/ NeuN + were previously observed in murine SVZ [78]. Our observation may suggest that TBI alters the migration pathway and the differentiation fate of NPCs in the SVZ, and that this effect is enhanced by treatment with CGP42112A.…”

Section: Cgp42112a Treatment Post-tbi Induces Neurogenesismentioning

confidence: 43%

Angiotensin Receptor Type 2 Activation Induces Neuroprotection and Neurogenesis After Traumatic Brain Injury

et al. 2014

View full text Add to dashboard Cite

Angiotensin II receptor type 2 (AT 2 ) agonists have been shown to limit brain ischemic insult and to improve its outcome. The activation of AT 2 was also linked to induced neuronal proliferation and differentiation in vitro. In this study, we examined the therapeutic potential of AT 2 activation following traumatic brain injury (TBI) in mice, a brain pathology that displays ischemia-like secondary damages. The AT 2 agonist CGP42112A was continuously infused immediately after closed head injury (CHI) for 3 days. We have followed the functional recovery of the injured mice for 35 days post-CHI, and evaluated cognitive function, lesion volume, molecular signaling, and neurogenesis at different time points after the impact. We found dose-dependent improvement in functional recovery and cognitive performance after CGP42112A treatment that was accompanied by reduced lesion volume and induced neurogenesis in the neurogenic niches of the brain and also in the injury region. At the cellular/molecular level, CGP42112A induced early activation of neuroprotective kinases protein kinase B (Akt) and extracellular-regulated kinases ½ (ERK½), and the neurotrophins nerve growth factor and brain-derived neurotrophic factor; all were blocked by treatment with the AT 2 antagonist PD123319. Our results suggest that AT 2 activation after TBI promotes neuroprotection and neurogenesis, and may be a novel approach for the development of new drugs to treat victims of TBI.

show abstract

Section: Cgp42112a Treatment Post-tbi Induces Neurogenesismentioning

confidence: 43%

Angiotensin Receptor Type 2 Activation Induces Neuroprotection and Neurogenesis After Traumatic Brain Injury

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Therapeutic effects of transplantation of mesenchymal stem cells (MSCs) into a murine model of AD have been reported [13,14,15,16,17]. These studies suggest that the transplantation of MSCs can stimulate neurogenesis in the brains of adult rodents.…”

Section: Introductionmentioning

confidence: 99%

“…These studies suggest that the transplantation of MSCs can stimulate neurogenesis in the brains of adult rodents. Transplantation of MSCs could facilitate functional recovery in animal models of neurological disorders by promoting neurogenesis, via either enhanced proliferation of endogenous neural stem cells in the subgranular zone of the dentate gyrus [14], or via increases in the proliferation and neural differentiation of newly generated cells in the subventricular zone [15]. However, the outcome of the therapeutic effects of MSCs on neurogenesis and recovery of brain function is not sufficient, and remains to be further improved.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease

Liu

Wang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Alzheimer's disease (AD) is one of the most common dementias among aged people, and is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits. So far, this is no cure for AD. A therapeutic effect of transplantation of mesenchymal stem cells (MSCs) into murine model of AD has been reported, but remains to be further improved. Brn-4 is a transcription factor that plays a critical role in neuronal development, whereas the effects of Brn-4 overexpression in transplanted MSCs on AD are unknown. Methods: MSCs were isolated from mouse bone marrow and induced to overexpress antisense of miRNA-937 (as-miR-937) through adeno-associated virus (AAV)-mediated transduction, and purified by flow cytometry based on expression of a GFP co-transgene in the cells. The Brn-4 levels in mouse MSCs were examined in miR-937-modified MSCs by RT-qPCR and by Western blot. These miR-937-modified MSCs were then transplanted into an APP/PS1 transgenic AD model in mice. The effects of saline control, MSCs and asmiR-937 MSCs on AD mice were examined by deposition of amyloid-beta peptide aggregates (Aβ), social recognition test (SR), Plus-Maze Discriminative Avoidance Task (PM-DAT) and the levels of Brain-derived neurotrophic factor (BDNF) in the mouse brain. Results: MSCs expressed high levels of Brn-4 transcripts but low levels of Brn-4 protein. Poor protein vs mRNA levels of Brn-4 in MSCs appeared to result from the presence of high levels of miR-937 in MSCs. miR-937 inhibited translation of Brn-4 mRNA through binding to the 3'-UTR of the Brn-4 mRNA in MSCs. Expression of as-miR-937 significantly increased Brn-4 protein levels in MSCs. Transplantation of as-miR-937-expressing MSCs significantly reduced the deposition of Aβ, increased the levels of BDNF, and significantly improved the appearance in SR and PM-DAT in AD mice. Conclusion: Overexpression of as-miR-937 in MSCs may substantially improve the therapeutic effects of MSCs on AD, possibly through augmenting Brn-4 levels in MSCs.

show abstract

“…Likewise, bone marrow-derived mesenchymal stem cell therapies hold promise for treatment of Parkinson's disease and multiple system atrophy, both of which are neurodegenerative disorders [Lee and Park, 2009]. It is generally thought that the trophic influences of bone marrow cells account for many of the clinical benefits of these transplants [Li et al, 2002;Kan et al, 2011], but a direct contribution of NSCs derived from bone marrow has not been ruled out.…”

Section: The Elephant In the Roommentioning

confidence: 99%

Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room

Beltz

Brenneis²,

Benton³

2016

Brain Behav Evol

View full text Add to dashboard Cite

The 1st-generation neural precursors in the crustacean brain are functionally analogous to neural stem cells in mammals. Their slow cycling, migration of their progeny, and differentiation of their descendants into neurons over several weeks are features of the neural precursor lineage in crayfish that also characterize adult neurogenesis in mammals. However, the 1st-generation precursors in crayfish do not self-renew, contrasting with conventional wisdom that proposes the long-term self-renewal of adult neural stem cells. Nevertheless, the crayfish neurogenic niche, which contains a total of 200-300 cells, is never exhausted and neurons continue to be produced in the brain throughout the animal's life. The pool of neural precursors in the niche therefore cannot be a closed system, and must be replenished from an extrinsic source. Our in vitro and in vivo data show that cells originating in the innate immune system (but not other cell types) are attracted to and incorporated into the neurogenic niche, and that they express a niche-specific marker, glutamine synthetase. Further, labeled hemocytes that undergo adoptive transfer to recipient crayfish generate cells in neuronal clusters in the olfactory pathway of the adult brain. These hemocyte descendants express appropriate neurotransmitters and project to target areas typical of neurons in these regions. These studies indicate that under natural conditions, the immune system provides neural precursors supporting adult neurogenesis in the crayfish brain, challenging the canonical view that ectodermal tissues generating the embryonic nervous system are the sole source of neurons in the adult brain. However, these are not the first studies that directly implicate the immune system as a source of neural precursor cells. Several types of data in mammals, including adoptive transfers of bone marrow or stem cells as well as the presence of fetal microchimerism, suggest that there must be a population of cells that are able to access the brain and generate new neurons in these species.

show abstract

Mesenchymal Stem Cells Stimulate Endogenous Neurogenesis in the Subventricular Zone of Adult Mice

Cited by 72 publications

References 54 publications

Angiotensin Receptor Type 2 Activation Induces Neuroprotection and Neurogenesis After Traumatic Brain Injury

Angiotensin Receptor Type 2 Activation Induces Neuroprotection and Neurogenesis After Traumatic Brain Injury

Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease

Adult Neurogenesis: Lessons from Crayfish and the Elephant in the Room

Contact Info

Product

Resources

About