scholarly journals The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

2013 ◽  
Vol 33 (5) ◽  
pp. 625-634 ◽  
Author(s):  
Vanessa Donega ◽  
Cindy TJ van Velthoven ◽  
Cora H Nijboer ◽  
Annemieke Kavelaars ◽  
Cobi J Heijnen
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Functional Integration ◽  
Neonatal Encephalopathy ◽  
Ischemic Insult ◽  
Cellular Mechanisms ◽  
Regenerative Capacity ◽  
Newborn Brain ◽  
Cerebral Ischemic ◽  
The Brain

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia–ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

scholarly journals Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals After Injury

2020 ◽  
Author(s):  
Batoul Ghaddar ◽  
Luisa Lübke ◽  
David COURET ◽  
Sepand Rastegar ◽  
Nicolas Diotel
Keyword(s):  
Stem Cells ◽  
Adult Neurogenesis ◽  
Brain Plasticity ◽  
Adult Zebrafish ◽  
Cellular Mechanisms ◽  
Regenerative Capacity ◽  
Brain Repair ◽  
Cellular Events ◽  
Similarities And Differences ◽  
The Brain

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

scholarly journals Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals after Injury

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 391
Author(s):  
Batoul Ghaddar ◽  
Luisa Lübke ◽  
David Couret ◽  
Sepand Rastegar ◽  
Nicolas Diotel
Keyword(s):  
Stem Cells ◽  
Adult Neurogenesis ◽  
Brain Plasticity ◽  
Adult Zebrafish ◽  
Cellular Mechanisms ◽  
Regenerative Capacity ◽  
Brain Repair ◽  
Cellular Events ◽  
Similarities And Differences ◽  
The Brain

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity, and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia, and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals, one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

scholarly journals Translational Research in Stem Cell Treatment of Neuromuscular Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Hakan Orbay ◽  
Hiroshi Mizuno
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Functional Integration ◽  
Neuromuscular Diseases ◽  
Pharmacological Treatments ◽  
Precursor Cell Line ◽  
Donor Cells ◽  
Significant Disability ◽  
New Treatment ◽  
Stem Cell Treatment

Neuromuscular diseases are a heterogeneous group of diseases that lead to significant disability in effected individuals. Pharmacological treatments failed to provide any significant improvement to date. Recently, the introduction of stem cells into the field of health sciences raised the hopes for a new treatment for neuromuscular diseases. In theory, stem cells, owing to their multilineage differentiation capacity, could differentiate into myofibers and neurons and replace the degenerated cells leading to recovery of the patients. Results obtained from the preclinical studies supported this theory. However, clinical trials with stem cells could not meet the expectations mainly because of early mortality, limited migration, and differentiation of the implanted cells. Modification of the stem cells before implantation, such as introduction of deficient genes or commitment to a precursor cell line provided little improvement. The biggest barrier to overcome for a successful of stem cell treatment, which also should be the focus of the future studies, is to increase the functional integration of the donor cells with the recipient tissues. Understanding the underlying pathogenic mechanisms of the neuromuscular diseases is essential to achieve this goal.

scholarly journals Insight Into the Mechanisms and the Challenges on Stem Cell-Based Therapies for Cerebral Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Huiyong Liu ◽  
Sydney Reiter ◽  
Xiangyue Zhou ◽  
Hanmin Chen ◽  
Yibo Ou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Potential Effect ◽  
Therapeutic Window ◽  
Ethical Challenges ◽  
Stroke Treatment ◽  
Lesion Core ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Strokes are the most common types of cerebrovascular disease and remain a major cause of death and disability worldwide. Cerebral ischemic stroke is caused by a reduction in blood flow to the brain. In this disease, two major zones of injury are identified: the lesion core, in which cells rapidly progress toward death, and the ischemic penumbra (surrounding the lesion core), which is defined as hypoperfusion tissue where cells may remain viable and can be repaired. Two methods that are approved by the Food and Drug Administration (FDA) include intravenous thrombolytic therapy and endovascular thrombectomy, however, the narrow therapeutic window poses a limitation, and therefore a low percentage of stroke patients actually receive these treatments. Developments in stem cell therapy have introduced renewed hope to patients with ischemic stroke due to its potential effect for reversing the neurological sequelae. Over the last few decades, animal tests and clinical trials have been used to treat ischemic stroke experimentally with various types of stem cells. However, several technical and ethical challenges must be overcome before stem cells can become a choice for the treatment of stroke. In this review, we summarize the mechanisms, processes, and challenges of using stem cells in stroke treatment. We also discuss new developing trends in this field.

Stem cell application in neurorehabilitation

2020 ◽  
pp. 169-184
Author(s):  
Sebastian Jessberger ◽  
Armin Curt ◽  
Roger A. Barker
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Adult Brain ◽  
Proper Function ◽  
Great Promise ◽  
Neuropsychiatric Diseases ◽  
Brain And Spinal Cord ◽  
The Brain

A number of diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of correct and functional neural networks. In the past, a variety of therapeutic strategies to rescue these systems have been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting endogenous or transplanting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention, along with in situ reprogramming, and opened up novel therapeutic avenues in the context of regenerative medicine. Here we review recent advances in our understanding of how endogenous stem cells may be a part of pathological processes in certain neuropsychiatric diseases and summarize recent clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS.

scholarly journals Designing stem cell niches for differentiation and self-renewal

2018 ◽  
Vol 15 (145) ◽  
pp. 20180388 ◽  
Author(s):  
Hannah Donnelly ◽  
Manuel Salmeron-Sanchez ◽  
Matthew J. Dalby
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Regulatory Networks ◽  
Regulatory Mechanisms ◽  
Great Promise ◽  
Regenerative Capacity ◽  
Cell Niche ◽  
Stem Cell Niches

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche . Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro . In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.

scholarly journals Emerging mechanisms of asymmetric stem cell division

2018 ◽  
Vol 217 (11) ◽  
pp. 3785-3795 ◽  
Author(s):  
Zsolt G. Venkei ◽  
Yukiko M. Yamashita
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Division ◽  
Asymmetric Cell Division ◽  
Binary Outcomes ◽  
Cellular Mechanisms ◽  
Asymmetric Cell Divisions ◽  
Cell Divisions ◽  
Dividing Cells ◽  
Stem Cell Division

The asymmetric cell division of stem cells, which produces one stem cell and one differentiating cell, has emerged as a mechanism to balance stem cell self-renewal and differentiation. Elaborate cellular mechanisms that orchestrate the processes required for asymmetric cell divisions are often shared between stem cells and other asymmetrically dividing cells. During asymmetric cell division, cells must establish asymmetry/polarity, which is guided by varying degrees of intrinsic versus extrinsic cues, and use intracellular machineries to divide in a desired orientation in the context of the asymmetry/polarity. Recent studies have expanded our knowledge on the mechanisms of asymmetric cell divisions, revealing the previously unappreciated complexity in setting up the cellular and/or environmental asymmetry, ensuring binary outcomes of the fate determination. In this review, we summarize recent progress in understanding the mechanisms and regulations of asymmetric stem cell division.

Molecular Integration Of HoxB4 and STAT3 For Self-Renewal Of Hematopoietic Stem Cells: A Model Of Molecular Convergence For Stemness

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2444-2444
Author(s):  
Il-Hoan Oh ◽  
Kim Tae-Min ◽  
Jae-Seung Shim
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Functional Integration ◽  
The Self ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Cell State ◽  
Stem Cell State

Abstract Multiple transcription factors (TFs) that regulate the self-renewal/stem cell state of hematopoietic stem cells (HSCs) have been identified, but understanding the molecular interplay of these TFs for their functional coordination remains a challenging issue. In this study, we investigated the functional integration and transcriptional coordination of STAT3 and HoxB4, which are TFs known to have similar effects on the self-renewal of HSCs. We found that while STAT3 (STAT3-C) or HoxB4 similarly enhanced the in vitro self-renewal and in vivo repopulating activities of HSCs, simultaneous transduction of both STAT3-C and HoxB4 did not have any additive enhancing effects. In contrast, the overexpression of HoxB4 caused a ligand-independent Tyr-phosphorylation in STAT3, and the inhibition of the STAT3 activity in HoxB4-overexpressing bone marrow cells significantly abrogated the enhancing effects of HoxB4 on both the bone marrow repopulation and maintenance of the undifferentiated state, revealing a molecular integration of these two TFs for HSC self-renewal. Expression microarray analysis revealed a significant overlap of the transcriptomes regulated by STAT3 and HoxB4 in undifferentiated hematopoietic cells. Moreover, a gene set enrichment analysis (GSEA) for TFs that can recapitulate the transcriptional changes induced by HoxB4 or STAT3 showed significant overlap in the candidate TFs. Interestingly, among these identified TFs were the puripotency-related genes, Oct-4 and Nanog. These results indicate the functional integration of tissue-specific TFs for HSC self-renewal and provide insights into the functional convergence of various TFs towards a conserved transcription program for the stem cell state. Disclosures: No relevant conflicts of interest to declare.

Stem cell application in neurorehabilitation

2015 ◽  
pp. 148-160
Author(s):  
Sebastian Jessberger ◽  
Armin Curt ◽  
Roger Barker
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Stem Cell ◽  
Adult Brain ◽  
Proper Function ◽  
Great Promise ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Significant Attention ◽  
Future Treatment Option

Several diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of neural networks. A�variety of therapeutic strategies to rescue these systems has been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention and opened up novel therapeutic avenues. Here, recent advances in our understanding of endogenous stem cells are reviewed and new clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS are summarized.

scholarly journals mRNA-Expression of ERα, ERβ, and PR in Clonal Stem Cell Cultures Obtained from Human Endometrial Biopsies

2011 ◽  
Vol 11 ◽  
pp. 1762-1769 ◽  
Author(s):  
A. N. Schüring ◽  
J. Braun ◽  
S. Wüllner ◽  
L. Kiesel ◽  
M. Götte
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Adult Stem Cells ◽  
Direct Stimulation ◽  
Regenerative Capacity ◽  
Endometrial Stem Cells ◽  
Proliferation And Differentiation ◽  
Clonal Cultures ◽  
Cell Niche

Background. Proliferation and differentiation of the endometrium are regulated by estrogen and progesterone. The enormous regenerative capacity of the endometrium is thought to be based on the activity of adult stem cells. However, information on endocrine regulatory mechanisms in human endometrial stem cells is scarce. In the present study, we investigated the expression of ERα, ERβ, and PR in clonal cultures of human endometrial stem cells derived from transcervical biopsies.Methods. Endometrial tissue of 11 patients was obtained by transcervical biopsy. Stromal cell suspensions were plated at clonal density and incubated for 15 days. Expression of ERα, ERβand PR was determined by qPCR prior to and after one cloning round, and normalized to 18 S rRNA expression.Results. Expression of ERαand ERβwas downregulated by 64% and 89%, respectively ( and ). In contrast, PR was not significantly downregulated, due to a more heterogenous expression pattern.Conclusions. Culture of human endometrial stroma cells results in a downregulation of ERαand ERβ, while expression of PR remained unchanged in our patient collective. These results support the hypothesis that stem cells may not be subject to direct stimulation by sex steroids, but rather by paracrine mechanisms within the stem cell niche.

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