Preclinical Challenges and Clinical Target of Nanomaterials in Regenerative Medicine

2018 ◽  
pp. 1402-1423
Author(s):  
Martin Reinhardt ◽  
Shibashish Giri ◽  
Augustinus Bader
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Organ Engineering ◽  
Cell Therapies ◽  
Existing Problems ◽  
Present Generation

Currently, practical application of nanotechnological approaches and stem cell therapies remains a challenge in both preclinical and clinical settings. Many existing problems in tissue engineering to organ engineering have been solved by the combined approaches of nanotechnology and stem cell biology, but significant barriers remain. Details about the role of various types of nanomaterial in preclinical and clinical research have been reviewed elsewhere, but scant information exists about the influence of nanomaterials on stem cell biology. Herein, the authors highlight the current advances of nanotechnological approaches for expansion, differentiations, harvesting, labeling, imagining, tissue engineering, and organ engineering of different types of stem cells. The preclinical outcome of in vitro and in vivo animal experimentations along with some examples of clinical outcomes of nanomaterials on stem cell research is the main focus of this chapter. This book chapter might be an impetus for the present generation of young scientists to revolutionize the coming generation of effective human healthcare.

Preclinical Challenges and Clinical Target of Nanomaterials in Regenerative Medicine

2015 ◽  
pp. 350-371
Author(s):  
Martin Reinhardt ◽  
Shibashish Giri ◽  
Augustinus Bader
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Organ Engineering ◽  
Cell Therapies ◽  
Existing Problems ◽  
Present Generation

Currently, practical application of nanotechnological approaches and stem cell therapies remains a challenge in both preclinical and clinical settings. Many existing problems in tissue engineering to organ engineering have been solved by the combined approaches of nanotechnology and stem cell biology, but significant barriers remain. Details about the role of various types of nanomaterial in preclinical and clinical research have been reviewed elsewhere, but scant information exists about the influence of nanomaterials on stem cell biology. Herein, the authors highlight the current advances of nanotechnological approaches for expansion, differentiations, harvesting, labeling, imagining, tissue engineering, and organ engineering of different types of stem cells. The preclinical outcome of in vitro and in vivo animal experimentations along with some examples of clinical outcomes of nanomaterials on stem cell research is the main focus of this chapter. This book chapter might be an impetus for the present generation of young scientists to revolutionize the coming generation of effective human healthcare.

The Role of Nucleophosmin In Hematopoietic Stem Cells and the Pathogenesis of Myelodysplastic Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 95-95 ◽  
Author(s):  
Keisuke Ito ◽  
Paolo Sportoletti ◽  
John G Clohessy ◽  
Grisendi Silvia ◽  
Pier Paolo Pandolfi
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Cell Biology ◽  
De Novo ◽  
Stem Cell Biology ◽  
Hematopoietic Stem

Abstract Abstract 95 Myelodysplastic syndrome (MDS) is an incurable stem cell disorder characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Nucleophosmin (NPM) is directly implicated in primitive hematopoiesis, the pathogenesis of hematopoietic malignancies and more recently of MDS. However, little is known regarding the molecular role and function of NPM in MDS pathogenesis and in stem cell biology. Here we present data demonstrating that NPM plays a critical role in the maintenance of hematopoietic stem cells (HSCs) and the transformation of MDS into leukemia. NPM is located on chromosome 5q and is frequently lost in therapy-related and de novo MDS. We have previously shown that Npm1 acts as a haploinsufficient tumor suppressor in the hematopoietic compartment and Npm1+/− mice develop a hematologic syndrome with features of human MDS, including increased susceptibility to leukemogenesis. As HSCs have been demonstrated to be the target of the primary neoplastic event in MDS, a functional analysis of the HSC compartment is essential to understand the molecular mechanisms in MDS pathogenesis. However, the role of NPM in adult hematopoiesis remains largely unknown as Npm1-deficiency leads to embryonic lethality. To investigate NPM function in adult hematopoiesis, we have generated conditional knockout mice of Npm1, using the Cre-loxP system. Analysis of Npm1 conditional mutants crossed with Mx1-Cre transgenic mice reveals that Npm1 plays a crucial role in adult hematopoiesis and ablation of Npm1 in adult HSCs leads to aberrant cycling and followed by apoptosis. Analysis of cell cycle status revealed that HSCs are impaired in their ability to maintain quiescence after Npm1-deletion and are rapidly depleted in vivo as well as in vitro. Competitive reconstitution assay revealed that Npm1 acts cell-autonomously to maintain HSCs. Conditional inactivation of Npm1 leads to an MDS phenotype including a profoundly impaired ability to differentiate into cells of the erythroid lineage, megakaryocyte dyspoiesis and centrosome amplification. Furthermore, Npm1 loss evokes a p53-dependent response and Npm1-deleted HSCs undergo apoptosis in vivo and in vitro. Strikingly, transfer of the Npm1 mutation into a p53-null background rescued the apoptosis of Npm1-ablated HSCs and resulted in accelerated transformation to an aggressive and lethal form of acute myeloid leukemia. Our findings highlight the crucial role of NPM in stem cell biology and identify a new mechanism by which MDS can progress to leukemia. This has important therapeutic implications for de novo MDS as well as therapy-related MDS, which is known to rapidly evolve to leukemia with frequent loss or mutation of TRP53. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Distinct Embryonic Origin and Injury Response of Resident Stem Cells in Craniofacial Muscles

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu Cheng ◽  
Bing Shi ◽  
Jingtao Li
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Injury Response ◽  
Limb Muscles ◽  
Resident Stem Cells ◽  
Embryonic Origin

Craniofacial muscles emerge as a developmental novelty during the evolution from invertebrates to vertebrates, facilitating diversified modes of predation, feeding and communication. In contrast to the well-studied limb muscles, knowledge about craniofacial muscle stem cell biology has only recently starts to be gathered. Craniofacial muscles are distinct from their counterparts in other regions in terms of both their embryonic origin and their injury response. Compared with somite-derived limb muscles, pharyngeal arch-derived craniofacial muscles demonstrate delayed myofiber reconstitution and prolonged fibrosis during repair. The regeneration of muscle is orchestrated by a blended source of stem/progenitor cells, including myogenic muscle satellite cells (MuSCs), mesenchymal fibro-adipogenic progenitors (FAPs) and other interstitial progenitors. Limb muscles host MuSCs of the Pax3 lineage, and FAPs from the mesoderm, while craniofacial muscles have MuSCs of the Mesp1 lineage and FAPs from the ectoderm-derived neural crest. Both in vivo and in vitro data revealed distinct patterns of proliferation and differentiation in these craniofacial muscle stem/progenitor cells. Additionally, the proportion of cells of different embryonic origins changes throughout postnatal development in the craniofacial muscles, creating a more dynamic niche environment than in other muscles. In-depth comparative studies of the stem cell biology of craniofacial and limb muscles might inspire the development of novel therapeutics to improve the management of myopathic diseases. Based on the most up-to-date literature, we delineated the pivotal cell populations regulating craniofacial muscle repair and identified clues that might elucidate the distinct embryonic origin and injury response in craniofacial muscle cells.

Advances in Dental Pulp Stem Cell Biology for Biomedical Engineering (Preprint)

2020 ◽  
Author(s):  
Sejin Bae ◽  
Byeonguk Kang ◽  
Hyungbin Lee ◽  
Harrison Luu ◽  
Eric Mullins ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Dental Pulp ◽  
Cell Biology ◽  
Primary Objective ◽  
Stem Cell Biology ◽  
Extrinsic Factors ◽  
Differentiation Potential

BACKGROUND Many studies in stem cell biology have demonstrated that dental pulp stem cells (DPSC) may be highly proliferative and capable of pluripotent differentiation into many different tissue types. Recent advances in stem cell research have outlined methods for directing in vitro or in vivo differentiation of DPSC - although much remains to be discovered. OBJECTIVE Based upon this information, the primary objective of this study was to understand the biology and biotechnology needed to more effectively direct DPSC differentiation. METHODS Previously collected and isolated samples of DPSC from an existing repository were used. Due to the use of previously collected, non-identifiable samples this protocol was granted exemption from Human Subjects review. Previously established stem cell biomarkers (Sox-2, Oct-4, NANOG) from each isolate were correlated with their proliferation rates or doubling times to categorize them into rapid, intermediate, or slow-dividing multipotent DPSC. Growth factors and other dental biomaterials were subsequently tested to evaluate DPSC responses in proliferation, viability and morphology. RESULTS Differential responses were observed among DPSC isolates to growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic protein (BMP-2), and biomaterials such as mineralized trioxide aggregates (MTA). The responsiveness of DPSC isolates did not correlate with any single factor but rather with a combination of proliferation rate and biomarker expression. CONCLUSIONS These data strongly suggest that some, but not all DPSC isolates are capable of a robust and significant in vitro response to differentiation stimuli, although this response is not universal. Although some biomarkers and phenotypes that distinguish and characterize these DPSC isolates may facilitate the ability to predict differentiation potential, more research is needed to determine the other intrinsic and extrinsic factors that may contribute to and modulate these DPSC responses for biotechnology and bioengineering applications. CLINICALTRIAL N/A (not applicable)

scholarly journals Toward Personalized Cell Therapies by Using Stem Cells: Seven Relevant Topics for Safety and Success in Stem Cell Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Fernando de Sá Silva ◽  
Paula Nascimento Almeida ◽  
João Vitor Paes Rettore ◽  
Claudinéia Pereira Maranduba ◽  
Camila Maurmann de Souza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Controversial Issues ◽  
Immunosuppressive Activity ◽  
Cell Therapies ◽  
Tumorigenic Potential ◽  
Wide Range

Stem cells, both embryonic and adult, due to the potential for application in tissue regeneration have been the target of interest to the world scientific community. In fact, stem cells can be considered revolutionary in the field of medicine, especially in the treatment of a wide range of human diseases. However, caution is needed in the clinical application of such cells and this is an issue that demands more studies. This paper will discuss some controversial issues of importance for achieving cell therapy safety and success. Particularly, the following aspects of stem cell biology will be presented: methods for stem cells culture, teratogenic or tumorigenic potential, cellular dose, proliferation, senescence, karyotyping, and immunosuppressive activity.

Realistic Prospects for Stem Cell Therapeutics

Hematology ◽  
2003 ◽  
Vol 2003 (1) ◽  
pp. 398-418 ◽  
Author(s):  
George Q. Daley ◽  
Margaret A. Goodell ◽  
Evan Y. Snyder
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Stem Cell Biology ◽  
Cell Therapies ◽  
The Media ◽  
New Treatment ◽  
Definition Of

Abstract Studies of the regenerating hematopoietic system have led to the definition of many of the fundamental principles of stem cell biology. Therapies based on a range of tissue stem cells have been widely touted as a new treatment modality, presaging an emerging new specialty called regenerative medicine that promises to harness stem cells from embryonic and somatic sources to provide replacement cell therapies for genetic, malignant, and degenerative conditions. Insights borne from stem cell biology also portend development of protein and small molecule therapeutics that act on endogenous stem cells to promote repair and regeneration. Much of the newfound enthusiasm for regenerative medicine stems from the hope that advances in the laboratory will be followed soon thereafter by breakthrough treatments in the clinic. But how does one sort through the hype to judge the true promise? Are stem cell biologists and the media building expectations that cannot be met? Which diseases can be treated, and when can we expect success? In this review, we outline the realms of investigation that are capturing the most attention, and consider the current state of scientific understanding and controversy regarding the properties of embryonic and somatic (adult) stem cells. Our objective is to provide a framework for appreciating the promise while at the same time understanding the challenges behind translating fundamental stem cell biology into novel clinical therapies.

Designing and Engineering Stem Cell Niches

MRS Bulletin ◽  
2010 ◽  
Vol 35 (8) ◽  
pp. 591-596 ◽  
Author(s):  
Ana I. Teixeira ◽  
Ola Hermanson ◽  
Carsten Werner
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Biology ◽  
Chemical Engineering ◽  
Polyglycolic Acid ◽  
Differentiated Cells ◽  
Extracellular Matrix Components ◽  
Stem Cell Niches

AbstractStem cells have received a lot of attention due to great promises in medical treatment, for example, by replacing lost and sick cells and re-constituting cell populations. There are several classes of stem cells, including embryonic, fetal, and adult tissue specific. More recently, the generation of so-called induced pluripotent stem (iPS) cells from differentiated cells has been established. Common criteria for all types of stem cells include their ability to self-renew and to retain their ability to differentiate in response to specific cues. These characteristics, as well as the instructive steering of the cells into differentiation, are largely dependent on the microenvironment surrounding the cells. Such “stem cell friendly” microenvironments, provided by structural and biochemical components, are often referred to as niches. Biomaterials offer attractive solutions to engineer functional stem cell niches and to steer stem cell state and fatein vitroas well asin vivo. Among materials used so far, promising results have been achieved with low-toxicity and biodegradable polymers, such as polyglycolic acid and related materials, as well as other polymers used as structural “scaffolds” for engineering of extracellular matrix components. To improve the efficiency of stem cell control and the design of the biomaterials, interfaces among stem cell research, developmental biology, regenerative medicine, chemical engineering, and materials research are rapidly developing. Here we provide an introduction to stem cell biology and principles of niche engineering and give an overview of recent advancements in stem cell niche engineering from two stem cell systems—blood and brain.

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