Biomedical subjects

P R Sanberg

Publications and source records attributed to P R Sanberg.

At least 19 recordsLinked to original sources

PubMed2006

Influence of retinoic acid and lithium on proliferation and dopaminergic potential of human NT2 cells.

Our laboratory is working with the human NTera2/D1 (NT2) cell line, which has properties similar to those of progenitor cells in the central nervous system (CNS). These neural-like precursor cells can differentiate into all three major lineages, neurons, astrocytes, and oligodendrocytes. The pure neuronal population, hNT neurons, possess characteristics of dopamine (DA) cells. First, we analyzed whether the retinoic acid (RA)-treated hNT neurons and the NT2 precursor cells expressed two transcription factors required for development of the midbrain DA neurons. We report that NT2 cells endogenously expressed Engrailed-1 and Ptx3, whereas RA-treated hNT neurons did not express Engrailed-1 or Ptx3. Next we examined the influence of lithium treatment on Engrailed-1 and Ptx3 as well as another critical transcription factor, Nurr1. Previous research has shown that lithium can mimic the Wnt pathway, which is important for the induction of these transcription factors. Finally, we investigated the effect of lithium treatment on the viability and proliferation of NT2 cells, because lithium has been shown to stimulate neurogenesis in adult neural precursors. Lithium treatment increased the viability and proliferation of NT2 cells. The expression of transcription factors essential for the induction and maintenance of the DA phenotype was not increased in NT2 after lithium treatment. We conclude that the NT2 cell line is an excellent in vitro model system for studying the influence of pharmalogical agents on proliferation, differentiation, and apoptosis of a human neural progenitor cell line.

Antineoplastic Agents↗

PubMed2006

Sertoli cells induce systemic donor-specific tolerance in xenogenic transplantation model.

Cell therapy is a potentially powerful tool in the treatment of many grave disorders including leukemia, immune deficiencies, autoimmune diseases, and diabetes. However, finding matched donors is challenging and recipients may suffer from the severe complications of systemic immune suppression. Sertoli cells, when cotransplanted with both allo- and xenograft tissues, promote graft acceptance in the absence of systemic immunosuppression. How Sertoli cells do this is not, as yet, clearly defined. We have examined the ability of Sertoli cells to produce systemic immune tolerance. For this purpose, Sertoli cells were injected into an otherwise normal C57/BL6 mouse host via the lateral tail vein. No other immunosuppressive protocols were applied. Six to 8 weeks posttransplantation, blood was collected for analysis of cytokine levels. Tolerance to donor cells was determined by mixed lymphocytic culture, and production of T-cell-dependent antibody was determined by an in vitro anti-sheep red blood cell plaque-forming assay. Results showed a marked modulation of immune cytokines in the transplanted mouse host and donor-specific transplantation tolerance was achieved. Tolerant mouse lymphocytes maintained a competent humoral antibody response. Additionally, C57/BL6 mice transplanted with rat Sertoli cells tolerated rat skin grafts significantly longer than control non-Sertoli cell transplanted mice. We conclude that systemic administration of rat Sertoli cells across xenogenic barrier induces transplantation tolerance without altering systemic immune competence. These data suggest that Sertoli cells may be used as a novel and potentially powerful tool in cell transplantation therapy.

Animals↗

PubMed2005

Behavioral alterations in Lewis rats following two-day continuous 3-nitropropionic acid administration.

The mitochondrial toxin, 3-nitropropionic acid (3-NP), produces motor dysfunction and striatal atrophy in rats. However, rat strain and method of administration may contribute to variability in the deficits caused by 3-NP toxicity. To evaluate this, changes in nocturnal spontaneous locomotor activity from chronic administration of 3-NP using an osmotic mini pump, were examined in the Lewis rats. Lewis rats were treated with 3-NP or saline for 2 days and behavior was tested daily for a 15 day period. Animals receiving 3-NP displayed significantly less spontaneous activity than animals in the saline group. 3-NP treated animals also weighed significantly less when compared to saline treated animals. These results demonstrate that even though there were no significant alterations in overt anatomical pathology, even short-term exposure to 3-NP produced significant effects. This short-term administration may present a potential paradigm for examination of sub-threshold neurotoxicity.

Animals↗

PubMed2005

Survival of rat or mouse ventral mesencephalon neurons after cotransplantation with rat sertoli cells in the mouse striatum.

Transplanting cells across species (xenotransplantation) for the treatment of Parkinson's disease has been considered an option to alleviate ethical concerns and shortage of tissues. However, using this approach leads to decreased cell survival; the xenografted cells are often rejected. Sertoli cells (SCs) are testis-derived cells that provide immunological protection to developing germ cells and can enhance survival of both allografted and xenografted cells. It is not clear whether these cells will maintain their immunosuppressive support of cografted cells if they are transplanted across species. In this study, we investigated the immune modulatory capacity of SCs and the feasibility of xenografting these cells alone or with allografted and xenografted neural tissue. Transplanting xenografts of rat SCs into the mouse striatum with either rat or mouse ventral mesencephalon prevented astrocytic infiltration of the graft site, although all transplants showed activated microglia within the core of the graft. Surviving tyrosine hydroxylase-positive neurons were observed in all conditions, but the size of the grafts was small at best. SCs were found at 1 and 2 weeks posttransplant. However, few SCs were found at 2 months posttransplant. Further investigation is under way to characterize the immune capabilities of SCs in a xenogeneic environment.

Animals↗

PubMed2004

Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?

Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural-derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic-derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three-drug treatment) animals. The triple-suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CD antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human-specific antibodies (anti-human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, "neuralization," and migratory features of HUCB-derived cells.

Age Factors↗

PubMed2004

Formation and structure of transplantable tissue constructs generated in simulated microgravity from Sertoli cells and neuron precursors.

Cell transplantation therapy for Parkinson's disease (PD) has received much attention as a potential treatment protocol for this neurodegenerative condition. Although there have been promising successes with this approach, it remains problematic, especially regarding the inability to provide immediate trophic support to the newly grafted cells and the inability to prevent acute and/or long-term graft rejection by the host. To address these issues of cell graftability, we have created a novel tissue construct from isolated rat Sertoli cells (SC) and the NTerra-2 immortalized human neuron precursor cell line (NT2) utilizing NASA-developed simulated microgravity technology. The two cell types were cocultured at a 1:4 (SC/NT2) ratio in the High Aspect Rotating Vessel (HARV) biochamber for 3 days, after which a disc-shaped aggregate (1-4 mm diameter) was formed. Sertoli neuron aggregated cells (SNAC) were collected by gravity sedimentation and processed either for light and electron microscopy or for fluorescent immunocytochemistry. Intra-SNAC clusters of SC and NT2 cells were identified by anti-human mitochondrial protein (huMT--specific for NT2 cells) and cholera toxin subunit B (CTb--specific for SC). There was little evidence of cell death throughout the aggregate and the absence of central necrosis, as might be expected in such a large aggregate in vitro. Ultrastructurally, SC did not express junctional modifications with NT2 cells nor with adjacent SC as is typical of SC in vivo and, in some protocols, in vitro. NT2 cells, however, showed distinct intercellular junction-like densities with adjacent NT2 cells, often defining canaliculi-like channels between the microvillus borders of the cells. The results show that the use of simulated microgravity coculture provides a culture environment suitable for the formation of a unique and viable Sertoli-NT2 (i.e., SNAC) tissue construct displaying intra-aggregate cellular organization. The structural integration of SC with NT2 cells provides a novel transplantable tissue source, which can be tested to determine if SC will suppress rejection of the grafted NT2 cells and provide for their short- and long-term trophic support in situ in the treatment of experimental PD.

Animals↗

PubMed2003

Intravenous versus intrastriatal cord blood administration in a rodent model of stroke.

Human umbilical cord blood (hUCB) is a rich source of hematopoietic stem cells that have been used to reconstitute immune cells and blood lineages. Cells from another hematopoietic source, bone marrow, have been found to differentiate into neural cells and are effective in the treatment of stroke. In this study, we administered hUCB cells intravenously into the femoral vein or directly into the striatum and assessed which route of cell administration produced the greatest behavioral recovery in rats with permanent middle cerebral artery occlusion (MCAO). All animals were immunosuppressed with cyclosporine (CSA). When spontaneous activity was measured using the Digiscan automated system, it was found to be significantly less when hUCB was transplanted 24 hr after stroke compared with nontransplanted, stroked animals (P < 0.01). Furthermore, behavioral recovery was similar with both striatal and femoral hUCB delivery. This is in contrast to the step test, in which significant improvements were found only after femoral delivery of the hUCB cells. In the passive avoidance test, transplanted animals learned the task faster than nontransplanted animals (P < 0.05). Together, these results suggest that hUCB transplantation may be an effective treatment for brain injuries, such as stroke, or neurodegenerative disorders. In addition, intravenous delivery may be more effective than striatal delivery in producing long-term functional benefits to the stroked animal.

Animals↗

PubMed2003

Reconstructive neurosurgery for Parkinson's disease: a systematic review and preliminary meta-analysis.

This systematic review and meta-analysis aimed to identify the determinants for best practice and establish current benchmarks for recovery following reconstructive neurosurgery for people with Parkinson's disease. Eleven studies reporting results for 95 grafted patients were selected on the grounds of using optimal surgical techniques and the Core Assessment Program for Intracerebral Transplantation (CAPIT) protocol for data collection. Consistent trends demonstrating high levels of recovery were identified on most outcome measures. Determinants for best practice were identified as selecting younger patients; using low dose immunosuppression; bilateral grafting; and employing strategies to ensure the quantity and viability of the grafted cells. Secondary analysis of data demonstrated a correlation of rho=0.666 (P<0.05) between increases in striatal dopaminergic activity and UPDRS Motor (off) scores. Overall effect size 'd' was found to be 1.129 UPDRS Motor (off) condition and 0.719 for UPDRS Total (off) condition. The design of the studies and the variable standards for reporting the data precluded the use of more powerful and accurate meta-analyses. It was recommended that the creation of a collaborative database would improve the extraction of data and allow for more powerful statistical analyses for evaluating the overall harm and benefits associated with reconstructive neurosurgery.

Brain Tissue Transplantation↗

PubMed2002

Bilateral human fetal striatal transplantation in Huntington's disease.

BACKGROUND: Transplanted striatal cells have been demonstrated to survive, grow, establish afferent and efferent connections, and improve behavioral signs in animal models of Huntington's disease (HD). OBJECTIVE: To evaluate feasibility and safety and to provide preliminary information regarding the efficacy of bilateral human fetal striatal transplantation in HD. METHODS: Seven symptomatic patients with genetically confirmed HD underwent bilateral stereotactic transplantation of two to eight fetal striata per side in two staged procedures. Tissue was dissected from the lateral half of the lateral ventricular eminence of donors 8 to 9 weeks postconception. Subjects received cyclosporine for 6 months. RESULTS: Three subjects developed subdural hemorrhages (SDHs) and two required surgical drainage. One subject died 18 months after surgery from probable cardiac arrhythmia secondary to severe atherosclerotic cardiac disease. Autopsy demonstrated clearly demarcated grafts of typical developing striatal morphology, with host-derived dopaminergic fibers extending into the grafts and no evidence of immune rejection. Other adverse events were generally mild and transient. Mean Unified HD Rating Scale (UHDRS) motor scores were 32.9 plus minus 6.2 at baseline and 29.7 plus minus 7.5 12 months after surgery (p = 0.24). Post-hoc analysis, excluding one subject who experienced cognitive and motor deterioration after the development of symptomatic bilateral SDHs, found that UHDRS motor scores were 33.8 plus minus 6.2 at baseline and 27.5 plus minus 5.2 at 12 months (p = 0.03). CONCLUSIONS: Transplantation of human fetal striatal cells is feasible and survival of transplanted cells was demonstrated. Patients with moderately advanced HD are at risk for SDH after transplantation surgery.

Adult↗

PubMed2002

Lack of NF-kappaB p50 exacerbates degeneration of hippocampal neurons after chemical exposure and impairs learning.

The roles of activated NF-kappaB subunits in the CNS remain to be discerned. Members of this family of transcription factors are essential to diverse physiological processes and can be activated by pathogens, stress, pharmacological agents, and trauma. We are particularly interested in long-term NF-kappaB activation and its involvement in neuroplastic changes in the brain resulting from acquisition of memory as well as injury. Here, we use lesioning by the limbic-specific neurotoxicant trimethyltin (TMT) as a model in which to examine activation of the NF-kappaB p50 subunit before, during, and after neuronal degeneration. Neurons in wild-type mice that survived TMT-induced injury contained activated p50 and did not label with Fluoro-Jade, a histochemical marker of degenerating neurons. Granule cells of the wild-type dentate gyrus subregion, an area particularly vulnerable to TMT-induced degeneration, contained less activated p50 protein than CA regions. We compared the extent of degeneration in wild-type and p50-null mice and found a fivefold increase in death of hippocampal neurons in mice lacking p50. The hippocampus is key to processes of learning and memory, and NF-kappaB has reported involvement in these processes. The enhanced hippocampal degeneration in p50-null mice prompted us to evaluate their basal learning abilities, and we discovered that difficulties in task acquisition were an additional consequence of p50 ablation. These results indicate that absence of p50 negatively modulates learning ability as well as hippocampal responsiveness to brain injury after a chemical-induced lesion.

Animals↗

PubMed2002

hNT neurons express an immunosuppressive protein that blocks T-lymphocyte proliferation and interleukin-2 production.

Ntera2/D1 cells had an A1 B8 Bw6 Cw7 DR3 DR52 major histocompatibility complex (MHC) genotype. Its neuronal derivative, hNT neurons, expressed A1 B8 Bw6 MHC class I molecules, but did not activate, and its hNT supernatant suppressed allogeneic mixed lymphocyte cultures (MLC) >98% (p<0.01), phytohemagglutinin (PHA)-activated T-cell proliferation >87% (p<0.01), even 48 h after stimulation, suppressed phorbol 12-myristate 13-acetate (PMA)/ionomycin-induced T-cell proliferation >99% (p<0.001), and reduced interleukin-2 (IL-2) production (p<0.01), while maintaining T cells in a quiescent G(0)/G(1) state without lowering their viability. This immunosuppressive activity was attributed to a 40-100-kDa anionic hNT protein with an isoelectric point of 4.8.

Brain Tissue Transplantation↗

PubMed2002

Mecamylamine (Inversine): an old antihypertensive with new research directions.

Mecamylamine (Inversine), the first orally available antihypertensive agent, is now rarely used. Although celebrated in the 1950s, mecamylamine fell out of favour because of its widespread ganglionic side effects at antihypertensive doses (30-90 mg/day). However, recent studies suggest that mecamylamine is very effective at relatively low doses (2.5-5 mg b.i.d.) for blocking the physiological effects of nicotine and improving abstinence rates in smoking cessation studies, particularly for women. When these lower doses of mecamylamine are given, patients do not experience the severity of side effects that made the drug unpopular for the treatment of hypertension. Tobacco smoking is a strong risk factor for cardiovascular morbidity, including accelerated atherosclerosis and increased risk of heart attacks. Though currently untested, the available evidence suggests that low-dose mecamylamine therapy might reduce blood pressure variability and atherogenetic lipid profile in smokers. With this in mind, mecamylamine should be an important research tool in the field of hypertension research, particularly in recalcitrant smokers with mild to moderate hypertension.

Antihypertensive Agents↗

PubMed2002

Nicotinic acetylcholine receptors as targets for antidepressants.

While the monoamine deficiency hypothesis of depression is still most commonly used to explain the actions of antidepressant drugs, a growing body of evidence has accumulated that is not adequately explained by the hypothesis. This article draws attention to contributions from another apparently common pharmacological property of antidepressant medications--the inhibition of nicotinic acetylcholine receptors (nAChR). Evidence is presented suggesting the hypercholinergic neurotransmission, which is associated with depressed mood states, may be mediated through excessive neuronal nicotinic receptor activation and that the therapeutic actions of many antidepressants may be, in part, mediated through inhibition of these receptors. In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders.

Antidepressive Agents↗

PubMed2002

A unique cytoplasmic marker for extratesticular Sertoli cells.

In the absence of a definitive cell marker for testis-derived Sertoli cells, their identification in cell culture or in Sertoli cell-facilitated cell transplantation protocols is difficult and limits the creditable evaluation of experimental results. However, the production by prepubertal Sertoli cells of Mullerian inhibiting substance (MIS) presents the possibility of specifically identifying extratesticular Sertoli cells as well as Sertoli cells in situ, by the immunodection of this unique glycoprotein. This study was designed to determine if isolated rat Sertoli cells could be identified by routine immunocytochemistry utilizing an antibody raised against MIS. Sertoli cells immunostained for MIS included Sertoli cells in situ and freshly isolated, cultured and cocultured Sertoli cells, and Sertoli cells structurally integrated with NT2 cells in simulated microgravity. Detection of MIS was also determined by Western blot analysis.

Animals↗

PubMed2001

Nicotine induced seizures blocked by mecamylamine and its stereoisomers.

Recent genetic research has shown that certain forms of epilepsy may arise from mutations in the genes encoding for the alpha7 and alpha4 neuronal nicotinic acetylcholine receptor (nAChR) ion channels. These receptors are also involved with the induction of nicotine-induced seizures. (+/-)-Mecamylamine (Inversine), a classic nAChR antagonist, potently inhibits nicotine-induced seizures. The purpose of the present study was to assess the inhibitory effects of (+/-)-mecamylamine and its stereoisomers on nicotine-induced seizures in male Sprague-Dawley rats. Rats received saline, (+/-)-mecamylamine, R-(-)-mecamylamine, or S-(+)-mecamylamine (s.c.) at doses of 0.1, 0.3, or 1.0 mg/kg 15 minutes prior to nicotine injection, 3.6 mg/kg (s.c.), an optimal dose for seizure induction. Rats were observed for 30 minutes with seizure latency, duration, and severity as primary measures and locomotor activity recorded as a secondary measure at 5-minute intervals. The results indicate that mecamylamine and each of its stereoisomers block nicotine-induced seizures in a dose-related manner and suggest that the S-(+/-)- mecamylamine isomer has inhibitory properties more similar to the racemic than to the R-(-)-mecamylamine isomer. The results of this study may be clinically important for the future design of novel anti-seizure medications.

Animals↗

PubMed2001

In vitro induction and in vivo expression of bcl-2 in the hNT neurons.

Bcl-2 encodes membrane-associated proteins that suppress programmed cell death in cells of various origins. Compelling evidence suggests that bcl-2 is also involved in neuronal differentiation and axonal regeneration. The human Neuro-Teratocarcinoma (hNT) neurons constitute a terminally differentiated human neuronal cell line that is derived from the Ntera-2/clone D1 (NT2) precursors upon retinoic acid (RA) treatment. After transplantation into the central nervous system (CNS), the hNT neurons survive, engraft, maintain their neuronal identity, and extend long neurite outgrowth. We were particularly interested in the intracellular determinants that confer these post-transplant characteristics to the hNT neurons. Thus, we asked whether the hNT neurons express bcl-2 after transplantation into the rat striatum and if RA induction of the neuronal lineage is mediated by bcl-2. The grafted hNT neurons were first identified using three different antibodies that recognize human-specific epitopes, anti-hMit, anti-hNuc, and NuMA. After a 1-month post-transplant survival time, NuMA immunostaining revealed that 12% of the hNT neurons survived the transplantation. These neurons extended long neuritic processes within the striatum, as demonstrated using the human-specific antibody against the midsize neurofilament subunit HO14. Importantly, we found that 85% of the implanted hNT neurons expressed bcl-2 and that the in vitro induction of the neuronal lineage from the NT2 precursors with RA resulted in an upregulation of bcl-2 expression. Together, these data suggest that the differentiation of the hNT neurons to a neuronal lineage could be mediated at least partially by bcl-2.

Animals↗

PubMed2001

Apoptosis in cultured hNT neurons.

Programmed cell death (apoptosis) is an important mechanism shaping the size of different cell populations within the developing nervous system. In our study we used the NT2/D1 clone originally established from the Ntera 2 cell line to investigate the baseline levels of apoptosis in cultured postmitotic hNT (NT2-N) neurons previously treated for 3, 4 or 5 weeks with retinoic acid (RA) and compared it with apoptosis in NT2 precursors unexposed to RA. First, we examined whether different lengths of exposure to RA might affect baseline apoptotic rate in differentiating hNT neurons. Second, we investigated whether cultured hNT neurons, previously shown to possess dopaminergic characteristics, would be preferentially affected by apoptosis. Using the terminal deoxynucleotidyl transferase (tdt)-labeling technique we found that the postmitotic hNT neuronal cells exposed to RA demonstrated significantly higher numbers of apoptotic cells (12.5-15.8%) in comparison to rapidly dividing NT2 precursor cell line (3.6-4.4%) at both studied (1 and 5 days in vitro, DIV) time points. Similar apoptotic nuclear morphology, including a variable extent of nuclear fragmentation was observed in all examined hNT cultures. On the other hand, the incidence of apoptotic nuclei was rare in cultures of NT2 precursors not subjected to RA treatment. Combined immunocytochemistry for tyrosine hydroxylase (TH) and Hoechst staining revealed dopaminergic hNT neurons destined to die. Our double-labeling studies have demonstrated that only a subset of TH-positive hNT cells had condensed chromatin after 1 (approx. 15%) and 5 (approx. 20%) DIV. NT2 precursors were not TH-positive. Collectively, our results demonstrated that exposure to differentiating agent RA triggers an apoptotic commitment in a subset of postmitotic hNT neurons. These results suggest that this cell line may serve as a model of neuronal development to test various pathogenic factors implicated in the etiology of Parkinson's disease (PD), as well as to screen numerous pharmacological treatments that may slow or prevent dopaminergic deterioration.

Antineoplastic Agents↗

PubMed2001

Comparison of calcium-binding proteins expressed in cultured hNT neurons and hNT neurons transplanted into the rat striatum.

An alternative source of cells for neural transplantation and brain repair that has many characteristics of immature neurons is the hNT neuron, derived from an embryonal human teratocarcinoma (NTera2) cell line that is terminally differentiated in vitro with retinoic acid. The majority of hNT neurons are GABAergic in cell culture. We have determined the calcium-binding protein (CBP) phenotypes of hNT neurons for three CBPs, calretinin (CR), calbindin D-28K (CB), and parvalbumin (PV), in cell culture and after transplantation into the rat striatum. In cell culture, 95% of all cell profiles were human nuclear matrix antigen (NuMA) positive. PV-positive hNT neurons constituted 50% of all neuron-like profiles, with CB+ and CR+ constituting 14 and 6% of cells, respectively. In contrast, when the striatal grafts were examined after 30 days survival using confocal microscopy, only 10% of hNT neurons immunopositive for NuMA were PV+; 19% were CB+/NuMA+, approximately the same percentage as was seen in vitro, and 82% of grafted hNT neurons were CR+. These results suggest that hNT neurons can be subdivided into at least three subpopulations based on the CBP phenotype that they express and that there is a CBP phenotypic shift following transplantation. Three related hypotheses are proposed to account for this phenotypic shift of hNT neurons after transplantation: (a) selective survival of the CR+ subpopulation of hNT neurons, (b) selective transitory quiescence of the transplanted PV+ cells due to transplantation stress, or (c) dedifferentiation of the hNT neurons following transplantation, which may allow them to respond to local environmental cues during the engraftment process.

Animals↗