scholarly journals Generation of Multipotent Stem Cells from Adult Human Peripheral Blood Following the Treatment with Platelet-Derived Mitochondria

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1350 ◽  
Author(s):  
Haibo Yu ◽  
Wei Hu ◽  
Xiang Song ◽  
Yong Zhao
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cellular Reprogramming ◽  
Multipotent Stem Cells ◽  
Functional Studies

Autologous stem cells are highly preferred for cellular therapy to treat human diseases. Mitochondria are organelles normally located in cytoplasm. Our recent studies demonstrated the differentiation of adult peripheral blood-derived insulin-producing cells (designated PB-IPC) into hematopoietic-like cells after the treatment with platelet-derived mitochondria. To further explore the molecular mechanism and their therapeutic potentials, through confocal and electron microscopy, we found that mitochondria enter cells and directly penetrate the nucleus of PB-IPC after the treatment with platelet-derived mitochondria, where they can produce profound epigenetic changes as demonstrated by RNA-seq and PCR array. Ex vivo functional studies established that mitochondrion-induced PB-IPC (miPB-IPC) can give rise to retinal pigment epithelium (RPE) cells and neuronal cells in the presence of different inducers. Further colony analysis highlighted the multipotent capability of the differentiation of PB-IPC into three-germ layer-derived cells. Therefore, these data indicate a novel function of mitochondria in cellular reprogramming, leading to the generation of autologous multipotent stem cells for clinical applications.

scholarly journals Generation of Hematopoietic-Like Stem Cells from Adult Human Peripheral Blood Following Treatment with Platelet-Derived Mitochondria

2020 ◽  
Vol 21 (12) ◽  
pp. 4249 ◽  
Author(s):  
Haibo Yu ◽  
Wei Hu ◽  
Xiang Song ◽  
Dante Descalzi-Montoya ◽  
Zheng Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Adult Stem Cells ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Embryonic Stem ◽  
Cellular Reprogramming ◽  
Hematopoietic Stem

Adult stem cells represent a potential source for cellular therapy to treat serious human diseases. We characterized the insulin-producing cells from adult peripheral blood (designated PB-IPC), which displayed a unique phenotype. Mitochondria are normally located in the cellular cytoplasm, where they generate ATP to power the cell’s functions. Ex vivo and in vivo functional studies established that treatment with platelet-derived mitochondria can reprogram the transformation of adult PB-IPC into functional CD34+ hematopoietic stem cells (HSC)-like cells, leading to the production of blood cells such as T cells, B cells, monocytes/macrophages, granulocytes, red blood cells, and megakaryocytes (MKs)/platelets. These findings revealed a novel function of mitochondria in directly contributing to cellular reprogramming, thus overcoming the limitations and safety concerns of using conventional technologies to reprogram embryonic stem (ES) and induced pluripotent stem (iPS) cells in regenerative medicine.

Abstract 17581: Evidence for Circulating Stem Cells Derived from the Human Heart and Their Therapeutic Potential

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Han-Mo Yang ◽  
Ju-Young Kim ◽  
Hyun-Jai Cho ◽  
Joo-Eun Lee ◽  
So-Jung Lim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Human Heart ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Heart Function ◽  
Human Peripheral Blood ◽  
Mouse Heart ◽  
Multipotent Stem Cells ◽  
Hematopoietic Stem

Introduction and Hypothesis: Many studies have shown resident cardiac stem cells in myocardium as well as epicardial progenitor cells in epicardium. However, the presence of stem cells in the endocardium has not been elucidated. In this study, we identified circulating multipotent stem cells from human peripheral blood. Furthermore, we investigated the origin and the therapeutic potential of these cells. Methods and Results: We identified a new population of cells from human peripheral blood mononuclear cells, which were quite different from previously reported stem cells. Newly identified cells expressed genes such as Oct3/4, KLF4, Nanog, and c-Myc. Moreover, FACS analysis precluded the possibility that these cells might be hematopoietic stem cells. To investigate the origin of these cells, we collected peripheral blood from patients undergoing bone marrow, liver, heart, or kidney transplantation. After culturing these cells, we could confirm that these stem cells were derived from the human heart by identifying the HLA types or the STR (short tandem repeat) profiles. In addition, we demonstrated that Nuclear Factor of Activated T-cells (NFAT)-positive and CD31-positive circulating cells in peripheral blood were derived from NFAT-positive cells in the endocardium. These cells had multipotency, indicating the ability of differentiation not only into mesodermal lineages, but also into ectodermal or endodermal lineages. When injected into the mouse heart in vivo , these stem cells were differentiated into multiple lineages, resulting in the improvement of the heart function. We established more than 200 cell lines from peripheral blood of patients with coronary artery diseases, cardiomyopathies, hematologic diseases, liver diseases, and kidney diseases. Conclusions: We demonstrated the existence of novel circulating multipotent stem cells in human peripheral blood, which express NFAT. Interestingly, these cells are derived from the tissue-resident stem cells of the endocardium of the human heart. Our findings suggest that these stem cells obtainable from peripheral blood could be a promising tool for heart regeneration.

scholarly journals Characterisation of multipotent stem cells from human peripheral blood using an improved protocol

2019 ◽  
Vol 19 ◽  
pp. 18-28 ◽  
Author(s):  
Weiping Lin ◽  
Liangliang Xu ◽  
Sien Lin ◽  
Liu Shi ◽  
Bin Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Multipotent Stem Cells

scholarly journals Ocular Toxoplasmosis: Mechanisms of Retinal Infection and Experimental Models

Parasitologia ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 50-60
Author(s):  
Veronica Rodriguez Fernandez ◽  
Giovanni Casini ◽  
Fabrizio Bruschi
Keyword(s):  
Ex Vivo ◽  
Cell Damage ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Treatment Strategies ◽  
Experimental Models ◽  
Ocular Toxoplasmosis ◽  
Cell Infection

Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii and affects many individuals throughout the world. Infection may occur through congenital or acquired routes. The parasites enter the blood circulation and reach both the retina and the retinal pigment epithelium, where they may cause cell damage and cell death. Different routes of access are used by T. gondii to reach the retina through the retinal endothelium: by transmission inside leukocytes, as free parasites through a paracellular route, or after endothelial cell infection. A main feature of OT is the induction of an important inflammatory state, and the course of infection has been shown to be influenced by the host immunogenetics. On the other hand, there is evidence that the T. gondii phenotype also has an impact on the distribution of the pathology in different areas. Although considerable knowledge has been acquired on OT, a deeper knowledge of its mechanisms is necessary to provide new, more targeted treatment strategies. In particular, in addition to in vitro and in vivo experimental models, organotypic, ex vivo retinal explants may be useful in this direction.

scholarly journals Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Angela Duong ◽  
Alesya Evstratova ◽  
Adam Sivitilli ◽  
J. Javier Hernandez ◽  
Jessica Gosio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Pluripotent Stem Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Induced Pluripotent

AbstractMitochondrial health plays a crucial role in human brain development and diseases. However, the evaluation of mitochondrial health in the brain is not incorporated into clinical practice due to ethical and logistical concerns. As a result, the development of targeted mitochondrial therapeutics remains a significant challenge due to the lack of appropriate patient-derived brain tissues. To address these unmet needs, we developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Our results show preserved mitochondrial genetics, function and treatment responses across PBMCs to iPSCs to COs, and measurable neuronal activity in the COs. We expect our approach will serve as a model for more widespread evaluation of mitochondrial health relevant to a wide range of human diseases using readily accessible patient peripheral (PBMCs) and stem-cell derived brain tissue samples.

Effects of glucocorticoids and mineralocorticoids on proliferation and maturation of human peripheral blood stem cells

1999 ◽  
Vol 62 (2) ◽  
pp. 65-73 ◽  
Author(s):  
St�phanie Grafte-Faure ◽  
Catherine Leveque ◽  
Marc Vasse ◽  
Claudine Soria ◽  
Vic Norris ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Peripheral Blood Stem Cells ◽  
Blood Stem Cells

scholarly journals Engineering Efficient Retinal Pigment Epithelium Differentiation From Human Pluripotent Stem Cells

2014 ◽  
Vol 3 (11) ◽  
pp. 1295-1304 ◽  
Author(s):  
Amelia Lane ◽  
Lissa Rachel Philip ◽  
Ludmila Ruban ◽  
Kate Fynes ◽  
Matthew Smart ◽  
...  
Keyword(s):  
Stem Cells ◽  
Retinal Pigment Epithelium ◽  
Pluripotent Stem Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Human Pluripotent Stem Cells
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