Do Bone Marrow Cells Generate Neurons?

Hess, David C.; Hill, W. David; Carroll, James E.; Borlongan, Cesario V.

doi:10.1001/archneur.61.4.483

Cited by 24 publications

(14 citation statements)

References 17 publications

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“…42 In this context, several studies have reported that BMDCs migrate into the brain, raising the possibility of using them as a new tool for the repair of damaged brain tissue. 43,44 In one of the first studies, Priller et al 9 demonstrated the neogenesis of cerebellar Purkinje neurons derived from BDMCs in vivo. They found fully developed Purkinje neurons after a long-term follow-up of 15 months post BMT in chimeric C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice

Pietzner¹,

Merscher²,

Baer³

et al. 2016

Bone Marrow Transplant

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Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a coconditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atmdeficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model.

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Section: Discussionmentioning

confidence: 99%

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice

Pietzner¹,

Merscher²,

Baer³

et al. 2016

Bone Marrow Transplant

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“…49 Stem cells There are three types of host-derived cells that have the potential to differentiate into neural tissues, neurons and/or glia. These are primitive bone marrow (BM) cells, which have the ability to differentiate into neurons, 50 olfactory ensheathing cells (OEC) and neural precursor cells (NPC), which lie within the matrix lining the cerebral ventricles, central canal of the spinal cord and in the dentate gyrus of the hippocampus. Because of their ability to differentiate and replace lost tissues, the undifferentiated resting cells in adult tissues have been referred to as a type of stem cell.…”

Section: Cellular Therapymentioning

confidence: 99%

Neuropathology: the foundation for new treatments in spinal cord injury

2004

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The first step essential in the search for a cure of human spinal cord injury (SCI) is to appreciate the complexity of the disorder. In this regard, it is not only the loss of ambulation but the sensory and autonomic changes that are equally important in recovery. In addition, there are the serious social emotional psychological and lifestyle effects of SCI which should also be taken into account. It is also true that no two SCI lesions are alike as each is the result of a SCI unique to that individual. Clinically of utmost importance is the segmental level of injury and whether it is complete, incomplete or discomplete (loss of all neurological functions below the injury but with physiological or anatomical continuity of Central nervous system tracts across the lesion). We are not concerned here with primary and secondary prevention or methods designed to limit the severity of the lesion after the event, important as they are, but with the requirements for a cure. Clearly, the greater the number of nerve fibers that can be preserved in the acute stage, the better will be the end result. Our focus at present is on the end-stage lesion with the aim of showing that a cure for SCI will depend upon establishing functionally useful central axonal regeneration and reestablishing physiological reconnections. Existing experimental methods are based on stimulating axonal regeneration by neutralizing inhibitory factors, adding positive trophisms and creating a permissive environment. Better results are obtained by bridging the gap with grafts of peripheral nerves or transplants of Schwann cells and genetically engineered fibroblasts. Recently, the potential for stem cells to enhance this process has created great interest. This is because of the ability of pluripotential cells to differentiate into neural tissue. A cure based on the physiopathology of SCI requires pyramidal, extrapyramidal, sensory, cerebellar and autonomic pathways to be regenerated with their appropriate neurotransmitters restored and reflexes integrated physiologically and in synchrony. In human SCI, there is a very long distance anatomically for axonal regrowth to occur in order to reach their relevant nuclei. This is because of continuing Wallerian degeneration. It also presumes that the target neurons are intact and that there has been no transneuronal degeneration above or below the lesion. Alternatively, in place of regenerated long axons, a multisynaptic pathway may be constructed from stem cells that have developed into neurons. Whether such a pathway would restore useful neurological functions is unknown. At present, the transplant and grafting research teams are exploring these possibilities in experimental animals. Moderate success in gaining axonal regeneration has been reported; however, it must be appreciated that the human lesion differs considerably from that of the experimental animal. In order to be successful, the neuropathology and neurophysiology of human SCI must be taken into account. The purpose of this review is to place the req...

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“…While the issue of transdifferentiation of stem cells has been the subject of much debate 13,14 , increased production of endogenous stem cells able to initiate tissue regeneration has been suggested as a mechanism for repair. 15 Pregnancy is an exemplary physiological condition in which a state of microchimerism between maternal and fetal stem cells can be evaluated. Despite the placental barrier, there is significant evidence that fetal cells and biomarkers can be detected in maternal blood during pregnancy and for several decades after delivery.…”

Section: Discussionmentioning

confidence: 99%

The effect of pregnancy on production of maternal endogenous hematopoietic stem cells

El‐Badri

Groer

2008

Bioscience Hypotheses

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SummaryFetal microchimerism refers to the presence of fetal cells in maternal blood and tissues during pregnancy. This microchimerism may result from trafficking of fetal and maternal blood across the placenta during pregnancy. Physiological changes in the maternal blood cellular milieu are also recognized during pregnancy and in the early post partum period. Earlier studies showed that maternal blood contains CD34 + hematopoietic stem cells (HSCs) that bear paternal genetic markers or male phenotype, suggesting that these cells circulated to the mother from male fetuses during pregnancy. Other studies showed that these maternal HSCs have significantly lower expansion potential than their fetal counterparts. We have recently shown increased percentages of CD34 + HSCs in peripheral blood of pregnant and parous women. Herein, we hypothesize that pregnancy stimulates the production of endogenous CD34 + HSCs of maternal origin, a phenomenon which potentially could favor post partum regenerative capacity.

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Do Bone Marrow Cells Generate Neurons?

Cited by 24 publications

References 17 publications

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice

Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice

Neuropathology: the foundation for new treatments in spinal cord injury

The effect of pregnancy on production of maternal endogenous hematopoietic stem cells

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