Tailoring the surface charge of dextran-based polymer coated SPIONs for modulated stem cell uptake and MRI contrast

Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and thein vivoenvironment facilitate and are required for the migration of MSCs to the site of insult or injuryin vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.

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Human levator veli palatini muscle: A novel source of mesenchymal stem cells for use in the rehabilitation of patients with congenital craniofacial malformations

10.21203/rs.3.rs-42456/v1 ◽

2020 ◽

Author(s):

Daniela Franco Bueno ◽

Gerson Shigueru Kabayashi ◽

Carla Cristina Gomes Pinheiro ◽

Daniela Y S Tanikawa ◽

Cassio Eduardo Raposo-Amaral ◽

...

Keyword(s):

Stem Cells ◽

Flow Cytometry ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Osteogenic Potential ◽

Flow Cytometry Analysis ◽

Non Invasive ◽

Levator Veli Palatini

Abstract Background. Bone reconstruction in congenital craniofacial differences, which affect about 2-3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stem cells in regenerative medicine protocols has opened a new field of investigation aimed at finding optimal sources of multipotent stem cells that can be isolated via non-invasive procedures. Here we analysed whether levator veli palatini muscle fragments, which can be readily obtained in non-invasive manner during surgical rehabilitation of cleft patients during palatoplasty, represent a novel source of MSCs with osteogenic potential. Methods. We obtained levator veli palatini muscle fragments, in non-invasive procedure during surgical rehabilitation of 5 unrelated cleft palate patients (palatoplasty surgery). The levator veli palatini muscle fragments was used to obtain the mesenchymal cells using pre-plating technique in a clean rooms infrastructure and all procedures were performed at good practices of manipulation conditions. To prove that levator veli palatini muscle are mesenchymal stem cells they were induced to flow cytometry analysis and to differentiation into bone, cartilage, fat and muscle. To demonstrate the osteogenic potential of these cells in vivo a bilateral full thickness calvarial defect model was made in immunocompentent rats.Results. Flow cytometry analysis showed that the cells were positive for mesenchymal stem cell antigens (CD29, CD73, CD90), while negative for hematopoietic (CD45) or endothelial cell markers (CD31). Moreover, these cells were capable of undergoing chondrogenic, adipogenic, osteogenic and skeletal muscle cell differentiation under appropriate cell culture conditions characterizing them as mesenchymal stem cell. Defects treated with CellCeramTM scaffolds seeded with levator veli palatini muscle cells showed significantly greater bone healing compared to defects treated with acellular scaffolds. Conclusion. We have demonstrated that cells derived from levator veli palatini muscle have phenotypic characteristics similar to other mesenchymal stem cells, both in vitro and in vivo. Our ﬁndings suggest that these cells may have clinical relevance in the rehabilitation of patients with cleft palate and other craniofacial anomalies characterized by significant bone deficit.

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Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine

Current Medicinal Chemistry ◽

10.2174/0929867328666210623142150 ◽

2021 ◽

Vol 28 ◽

Author(s):

Sanjeev Gautam ◽

Sangita Biswas ◽

Birbal Singh ◽

Ying Guo ◽

Peng Deng ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Drug Testing ◽

Diagnostic Tools ◽

Cell Therapies ◽

Non Invasive ◽

Key Issues ◽

Induced Pluripotent

: There is a momentous surge in the development of stem cell technology as a therapeutic and diagnostic tools. Stem cell-derived cells are currently used in various clinical trials. However, key issues and challenges involve the low differentiation efficiency, integration, and functioning of transplanted stem cells-derived cells. Extraction of bone marrow, adipose, or other mesenchymal stem cells (MSCs) involves invasive methods, specialized skills, and expensive technologies. Urine-derived cells, on the other hand, are obtained by non-invasive methods. Samples can be obtained repeatedly from patients of any age. Urine-derived cells are used to generate reprogrammed or induced pluripotent stem cells (iPSCs), which can be cultured, and differentiated into various types of cell lineages for biomedical investigations and drug testing in vitro or in vivo using model animals of human diseases. Urine cell-derived iPSCs (UiPSCs) have emerged as a major area of research and immense therapeutic significance. Given that preliminary preclinical studies are successful in terms of safety and as a regenerative tool, the UiPSCs will pave the way to develop and expedite various types of autologous stem cell therapies.

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A Novel Mouse Model for Non-Invasive Single Marker Tracking of Mammary Stem Cells In Vivo Reveals Stem Cell Dynamics throughout Pregnancy

PLoS ONE ◽

10.1371/journal.pone.0008035 ◽

2009 ◽

Vol 4 (11) ◽

pp. e8035 ◽

Cited By ~ 14

Author(s):

Benjamin J. Tiede ◽

Leah A. Owens ◽

Feng Li ◽

Christina DeCoste ◽

Yibin Kang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Mouse Model ◽

Mammary Stem Cells ◽

Cell Dynamics ◽

Marker Tracking ◽

Non Invasive ◽

Mammary Stem ◽

Single Marker

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Stem Cell Cure for Kidney Injury: Therapy to Solve Most Complex Issues in Renal System

Journal of Regenerative Biology and Medicine ◽

10.37191/mapsci-2582-385x-2(4)-038 ◽

2020 ◽

Author(s):

Prithiv K R Kumar

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Kidney Injury ◽

Cell Types ◽

Tissue Remodelling ◽

Major Health Problem ◽

In Vivo Experiments ◽

Renal Regeneration ◽

Induced Pluripotent

Renal failure is a major health problem. The mortality rate remain high despite of several therapies. The most complex of the renal issues are solved through stem cells. In this review, different mechanism for cure of chronic kidney injury along with cell engraftment incorporated into renal structures will be analysed. Paracrine activities of embryonic or induced Pluripotent stem cells are explored on the basis of stem cell-induced kidney regeneration. Several experiments have been conducted to advance stem cells to ensure the restoration of renal functions. More vigour and organised protocols for delivering stem cells is a possibility for advancement in treatment of renal disease. Also there is a need for pressing therapies to replicate the tissue remodelling and cellular repair processes suitable for renal organs. Stem cells are the undifferentiated cells that have the ability to multiply into several cell types. In vivo experiments on animal’s stem cells have shown significant improvements in the renal regeneration and functions of organs. Nevertheless more studies show several improvements in the kidney repair due to stem cell regeneration.

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Regulation of sarcomagenesis by the empty spiracles homeobox genes EMX1 and EMX2

Cell Death and Disease ◽

10.1038/s41419-021-03801-w ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Manuel Pedro Jimenez-García ◽

Antonio Lucena-Cacace ◽

Daniel Otero-Albiol ◽

Amancio Carnero

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Transcription Factors ◽

Neural Crest ◽

Tumor Suppressors ◽

Homeobox Genes ◽

Neuronal Cell ◽

Cell Gene Expression

AbstractThe EMX (Empty Spiracles Homeobox) genes EMX1 and EMX2 are two homeodomain gene members of the EMX family of transcription factors involved in the regulation of various biological processes, such as cell proliferation, migration, and differentiation, during brain development and neural crest migration. They play a role in the specification of positional identity, the proliferation of neural stem cells, and the differentiation of certain neuronal cell phenotypes. In general, they act as transcription factors in early embryogenesis and neuroembryogenesis from metazoans to higher vertebrates. The EMX1 and EMX2’s potential as tumor suppressor genes has been suggested in some cancers. Our work showed that EMX1/EMX2 act as tumor suppressors in sarcomas by repressing the activity of stem cell regulatory genes (OCT4, SOX2, KLF4, MYC, NANOG, NES, and PROM1). EMX protein downregulation, therefore, induced the malignance and stemness of cells both in vitro and in vivo. In murine knockout (KO) models lacking Emx genes, 3MC-induced sarcomas were more aggressive and infiltrative, had a greater capacity for tumor self-renewal, and had higher stem cell gene expression and nestin expression than those in wild-type models. These results showing that EMX genes acted as stemness regulators were reproduced in different subtypes of sarcoma. Therefore, it is possible that the EMX genes could have a generalized behavior regulating proliferation of neural crest-derived progenitors. Together, these results indicate that the EMX1 and EMX2 genes negatively regulate these tumor-altering populations or cancer stem cells, acting as tumor suppressors in sarcoma.

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“Empowering” Cardiac Cells via Stem Cell Derived Mitochondrial Transplantation- Does Age Matter?

International Journal of Molecular Sciences ◽

10.3390/ijms22041824 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1824

Author(s):

Matthias Mietsch ◽

Rabea Hinkel

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Treatment Strategies ◽

Cardiac Cells ◽

Aging Effects ◽

Beneficial Effects ◽

Micro Rnas ◽

New Treatment

With cardiovascular diseases affecting millions of patients, new treatment strategies are urgently needed. The use of stem cell based approaches has been investigated during the last decades and promising effects have been achieved. However, the beneficial effect of stem cells has been found to being partly due to paracrine functions by alterations of their microenvironment and so an interesting field of research, the “stem- less” approaches has emerged over the last years using or altering the microenvironment, for example, via deletion of senescent cells, application of micro RNAs or by modifying the cellular energy metabolism via targeting mitochondria. Using autologous muscle-derived mitochondria for transplantations into the affected tissues has resulted in promising reports of improvements of cardiac functions in vitro and in vivo. However, since the targeted treatment group represents mainly elderly or otherwise sick patients, it is unclear whether and to what extent autologous mitochondria would exert their beneficial effects in these cases. Stem cells might represent better sources for mitochondria and could enhance the effect of mitochondrial transplantations. Therefore in this review we aim to provide an overview on aging effects of stem cells and mitochondria which might be important for mitochondrial transplantation and to give an overview on the current state in this field together with considerations worthwhile for further investigations.

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Induced Pluripotent Stem Cells (iPSCs) in Vascular Research: from Two- to Three-Dimensional Organoids

Stem Cell Reviews and Reports ◽

10.1007/s12015-021-10149-3 ◽

2021 ◽

Author(s):

Anja Trillhaase ◽

Marlon Maertens ◽

Zouhair Aherrahrou ◽

Jeanette Erdmann

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Induced Pluripotent Stem Cells ◽

Stem Cell Research ◽

Pluripotent Stem Cells ◽

Embryonic Stem ◽

Cell Types ◽

3D Models ◽

Induced Pluripotent

AbstractStem cell technology has been around for almost 30 years and in that time has grown into an enormous field. The stem cell technique progressed from the first successful isolation of mammalian embryonic stem cells (ESCs) in the 1990s, to the production of human induced-pluripotent stem cells (iPSCs) in the early 2000s, to finally culminate in the differentiation of pluripotent cells into highly specialized cell types, such as neurons, endothelial cells (ECs), cardiomyocytes, fibroblasts, and lung and intestinal cells, in the last decades. In recent times, we have attained a new height in stem cell research whereby we can produce 3D organoids derived from stem cells that more accurately mimic the in vivo environment. This review summarizes the development of stem cell research in the context of vascular research ranging from differentiation techniques of ECs and smooth muscle cells (SMCs) to the generation of vascularized 3D organoids. Furthermore, the different techniques are critically reviewed, and future applications of current 3D models are reported. Graphical abstract

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Set1 Targets Genes with Essential Identity and Tumor-Suppressing Functions in Planarian Stem Cells

Genes ◽

10.3390/genes12081182 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1182

Author(s):

Prince Verma ◽

Court K. M. Waterbury ◽

Elizabeth M. Duncan

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Mammalian Cells ◽

Cell Function ◽

Genotoxic Stress ◽

Specific Gene ◽

Cell Identity ◽

Chromatin Signature ◽

Lysine Methyltransferase

Tumor suppressor genes (TSGs) are essential for normal cellular function in multicellular organisms, but many TSGs and tumor-suppressing mechanisms remain unknown. Planarian flatworms exhibit particularly robust tumor suppression, yet the specific mechanisms underlying this trait remain unclear. Here, we analyze histone H3 lysine 4 trimethylation (H3K4me3) signal across the planarian genome to determine if the broad H3K4me3 chromatin signature that marks essential cell identity genes and TSGs in mammalian cells is conserved in this valuable model of in vivo stem cell function. We find that this signature is indeed conserved on the planarian genome and that the lysine methyltransferase Set1 is largely responsible for creating it at both cell identity and putative TSG loci. In addition, we show that depletion of set1 in planarians induces stem cell phenotypes that suggest loss of TSG function, including hyperproliferation and an abnormal DNA damage response (DDR). Importantly, this work establishes that Set1 targets specific gene loci in planarian stem cells and marks them with a conserved chromatin signature. Moreover, our data strongly suggest that Set1 activity at these genes has important functional consequences both during normal homeostasis and in response to genotoxic stress.

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Enhancing therapeutic effects and in vivo tracking of adipose tissue derived mesenchymal stem cells for liver injury using bioorthogonal click chemistry

Nanoscale ◽

10.1039/d0nr07272a ◽

2020 ◽

Author(s):

Naishun Liao ◽

Da Zhang ◽

Ming Wu ◽

Huang-Hao Yang ◽

Xiaolong Liu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Stem Cell ◽

Liver Injury ◽

Mesenchymal Stem Cell ◽

Liver Diseases ◽

Therapeutic Effects

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...

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