scholarly journals Stem cells: Haemobiology and clinical data summarising: A critical review

2020 ◽  
Vol 51 (4) ◽  
pp. 261-271
Author(s):  
Bela Balint ◽  
Mirjana Pavlović ◽  
Milena Todorović
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Stromal Cells ◽  
Engineering Systems ◽  
Therapeutic Approaches ◽  
Self Renewal ◽  
Freeze Thaw ◽  
Differentiated Cells ◽  
Graft Engineering ◽  
Different Tissues

Stem cells (SC) are the unique and "key-cells" in the human body "working" as a source of producing a large number (proliferation) of mature (differentiation) cells inside different tissues ("cytopoiesis") - while at the same time maintaining the ability to "reproduce" themselves (self-renewal). These events are balanced by interactive signals from the extracellular matrix, as well as microenvironment provided by stromal cells. On the other hand, SC plasticity (so-called "inter-systemic plasticity") is the ability of the most "primitive" (immature) adult SCs to switch to novel identities. The phrase SC plasticity also involves phenotypic potential of these cells, broader than spectrum of phenotypes of differentiated cells in their original tissues. Recent increasing clinical use of cell-mediated therapeutic approaches has resulted in enlarged needs for both, higher quantity of SCs and improved operating procedures during extracorporeal manipulations. The aim of harvesting procedures is to obtain the best SC yield and viability. The goal of optimised cryopreservation is to minimise cellular thermal damages during freeze/thaw process (cryoinjury). Despite the fact that different SC collection, purification and cryopreservation protocols are already in routine use - a lot of problems related to the optimal SC extracorporeal manipulations are still unresolved. The objective of this paper is to provide an integral review of early haemobiological and cryobiological research in the unlimited "SC-field" with emphasis on their entities, recent cell-concepts, extracorporeal manipulative and "graft-engineering" systems. Their therapeutic relevance and efficacy in "conventional" SC transplants or regenerative medicine will be briefly summarised. Finally, in this paper original results will not be pointed out - related to neither SC transplants nor regenerative medicine - but a light will be shed on some of them.

scholarly journals Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Francesco Perdisa ◽  
Natalia Gostyńska ◽  
Alice Roffi ◽  
Giuseppe Filardo ◽  
Maurilio Marcacci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Clinical Evidence ◽  
Cartilage Regeneration ◽  
Therapeutic Approaches ◽  
Differentiated Cells ◽  
Cartilage Disease

Among the current therapeutic approaches for the regeneration of damaged articular cartilage, none has yet proven to offer results comparable to those of native hyaline cartilage. Recently, it has been claimed that the use of mesenchymal stem cells (MSCs) provides greater regenerative potential than differentiated cells, such as chondrocytes. Among the different kinds of MSCs available, adipose-derived mesenchymal stem cells (ADSCs) are emerging due to their abundancy and easiness to harvest. However, their mechanism of action and potential for cartilage regeneration are still under investigation, and many other aspects still need to be clarified. The aim of this systematic review is to give an overview ofin vivostudies dealing with ADSCs, by summarizing the main evidence for the treatment of cartilage disease of the knee.

Environmental Cues Can Promote Symmetrical Division of Functional Human Hematopoietic Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1397-1397
Author(s):  
Nadim Mahmud ◽  
Kazumi Yoshinaga ◽  
Craig Beam ◽  
Hiroto Araki
Keyword(s):  
Stem Cells ◽  
Cell Division ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Absolute Number ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Differentiated Cells ◽  
Cd34 Cells ◽  
Cells Cultured

Abstract Widespread clinical use of ex-vivo expanded human umbilical cord blood (CB) grafts has been limited by lack of proper understanding of factors regulating self-renewal type of symmetric cell divisions. The expansion of the number of functional hematopoietic stem cells (HSC) ex-vivo requires the creation of an environment which favors symmetrical division. In our current studies, addition of late acting cytokines, (GM-CSF, IL-6, Epo) with early acting cytokines (thrombopoietin, SCF, Flt-3 ligand) resulted in loss of expansion of stem/progenitor cells. These data indicate that modification of HSC fate is not fully independent of external humoral influences. We have previously demonstrated that following treatment of CD34+ cells with 5-aza-2-deoxycytidine (5azaD) and trichostatin A (TSA) there is a 10- fold increase in the number of SCID mouse repopulating cells (SRC). This increase of SRC, however, occurred concomitantly with an increase in absolute number of CD34+CD90+ cells as well as primitive progenitors which gives rise to colony forming unit Mix lineage (CFU-Mix). We hypothesized that if the primary CD34+ cells generates CFU-Mix/CFU-GM in a ratio of ‘X’, then to observe a higher rate of symmetric cell division we would expect to see the ratio increased (>X) in the 5azaD/TSA treated cells in comparison to cells cultured in the absence of 5azaD/TSA (< X). Interestingly, analyses of our data suggest that when 5azaD/TSA treated CD34+ cells are cultured for 5 days and assayed for colonies we observed a significant increase in the ratio of CFU-Mix/CFU-GM in contrast to cells cultured in cytokines alone, 0.373 ± 0.06 and 0.066 ± 0.032 respectively. The ratio of CFU-Mix/CFU-GM of CB CD34+ cells (day 0) was 0.262 ± 0.045. These findings indicate that 5azaD/TSA treatment promotes the ratio of CFU-Mix/CFU-GM possibly by enhancing symmetric division of CFU-Mix while in the absence of 5azaD/TSA treatment the culture condition likely induces differentiation. In addition, we have also investigated the ratio of progenitor cells/differentiated cells by assessing the ratio of human CD34+ cells/CD33+ cells in the bone marrow of immunodeficient mice following transplantation (8 weeks) of equal numbers of CD34+ cells. The ratio of CD34+ cells/CD33+ cells following transplantation of 5azaD/TSA treated cells was 0.52 ± 0.14 (n = 11) while in the absence of 5azaD/TSA the ratio dropped to 0.31± 0.16 (n = 4). The ratio following transplantation of primary CD34+ (day 0) cells was 0.62 ± 0.14 (n = 6). These data suggest that 5azaD/TSA treated cells maintain the balance of generation of CD34+ cells/CD33+ cells at a comparable rate to that of primary CD34+ cells, while the CD34+ cells generated in the absence of 5azaD/TSA promotes generation of more differentiated cells. Alternatively, it is also possible that 5azaD/TSA treatment of CD34+ cells in the culture results in inhibition of myeloid differentiation at the cost of proliferation. However, the latter possibility is unlikely, since treatment of CB cells with 5azaD/TSA results in an increase in the absolute number of progenitors including SRC possessing both myeloid and lymphoid differentiation potential. Taken together, these data support our hypothesis that chromatin modifying agents in the culture is capable of promoting self-renewal type of symmetric cell division possessing in vivo multilineage marrow repopulating potential.

scholarly journals Cancer Stem Cells and Their Microenvironment: Biology and Therapeutic Implications

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Eunice Yuen-Ting Lau ◽  
Nicole Pui-Yu Ho ◽  
Terence Kin-Wah Lee
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Stromal Cells ◽  
Stem Cell Niche ◽  
Therapeutic Resistance ◽  
Physical Factors ◽  
Self Renewal ◽  
Therapeutic Implications ◽  
Cell Niche ◽  
Tumor Stiffness

Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs) that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance. With a better understanding of how CSC interacts with its niche, we are able to identify potential therapeutic targets for the development of more effective treatments against cancer.

scholarly journals Serum-Free Manufacturing of Mesenchymal Stem Cell Tissue Rings Using Human-Induced Pluripotent Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tackla S. Winston ◽  
Kantaphon Suddhapas ◽  
Chenyan Wang ◽  
Rafael Ramos ◽  
Pranav Soman ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Culture Conditions ◽  
Serum Free ◽  
Differentiated Cells ◽  
Induced Pluripotent

Combination of stem cell technology and 3D biofabrication approaches provides physiological similarity to in vivo tissues and the capability of repairing and regenerating damaged human tissues. Mesenchymal stem cells (MSCs) have been widely used for regenerative medicine applications because of their immunosuppressive properties and multipotent potentials. To obtain large amount of high-quality MSCs without patient donation and invasive procedures, we differentiated MSCs from human-induced pluripotent stem cells (hiPSC-MSCs) using serum-free E6 media supplemented with only one growth factor (bFGF) and two small molecules (SB431542 and CHIR99021). The differentiated cells showed a high expression of common MSC-specific surface markers (CD90, CD73, CD105, CD106, CD146, and CD166) and a high potency for osteogenic and chondrogenic differentiation. With these cells, we have been able to manufacture MSC tissue rings with high consistency and robustness in pluronic-coated reusable PDMS devices. The MSC tissue rings were characterized based on inner diameter and outer ring diameter and observed cell-type-dependent tissue contraction induced by cell-matrix interaction. Our approach of simplified hiPSC-MSC differentiation, modular fabrication procedure, and serum-free culture conditions has a great potential for scalable manufacturing of MSC tissue rings for different regenerative medicine applications.

Stem Cell-Based Personalized Medicine

2012 ◽  
pp. 1855-1866
Author(s):  
Alessandro Prigione
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Personalized Medicine ◽  
Regenerative Medicine ◽  
Cell Types ◽  
Research Field ◽  
Cellular Reprogramming ◽  
Differentiated Cells ◽  
New Therapeutic Approaches

Regenerative medicine is a rapidly evolving research field whose main aims are to provide new therapeutic approaches and to repair or replace injured tissues with functional cells derived from stem cells. In the past few years, research breakthroughs have revolutionized the field by showing that all somatic cells have the potential to re-acquire stem cell-like properties. Thus, it appears possible to generate relevant cell types starting from cells easily obtained from affected individuals. The obtained differentiated cells could eventually serve as in vitro tools for the study of disease-associated mechanisms and for performing customized drug screenings. Moreover, in the context of cellular transplantation, these cells represent the ideal cell source given that they posses the same genetic code and thus will avoid the occurrence of unwanted immune reactions. Overall, this revolutionary technique called cellular reprogramming might provide substantial support for the future development of personalized medicine. In this chapter, I describe the recent advances in the field of stem cell-based regenerative medicine applications. Parkinson’s disease is chosen as a paradigmatic example in which the use of stem cells for study and therapy could have a relevant impact and potentially represent a future cure for this debilitating disorder.

Secreted Mediators of Self-Renewal of Hematopoietic Stem Cells Identified Using Bio-Informatic Analysis of Co-Cultures of HSC and Stromal Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2353-2353
Author(s):  
Baiba Vilne ◽  
Rouzanna Istvanffy ◽  
Christina Eckl ◽  
Franziska Bock ◽  
Olivia Prazeres da Costa ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Cell Division ◽  
Hematopoietic Stem Cells ◽  
Stromal Cells ◽  
Tissue Growth ◽  
Functional Enrichment ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
A Cell

Abstract Abstract 2353 Hematopoiesis is maintained throughout life by the constant production of mature blood cells from hematopoietic stem cells (HSC). One mechanism by which the number of HSC is maintained is self-renewal, a cell division in which at least one of the daughter cells is a cell with the same functional potential as the mother cell. The mechanisms of this process are largely unknown. We have described cell lines that maintain self-renewal in culture. To study possible mechanisms and mediators involved in self-renewal, we performed co-cultures of HSC model cells: Lineage-negative Sca-1+ c-Kit+ (LSK) cells and HSC maintaining UG26–1B6 stromal cells. Microarray analyses were performed on cells prior to co-culture and cells sorted from the cultures. STEM clustering analysis of the data revealed that most changes in gene expression were due to early cell activation. Functional enrichment analysis revealed dynamic changes in focal adhesion and mTOR signaling, as well as changes in epigenetic regulators, such as HDAC in stromal cells. In LSK cells, genes whose products are involved in inflammation, Oxygen homeostasis and metabolism were differentially expressed after the co-culture. In addition, genes involved in the regulaton of H3K27 methylation were also affected. Interestingly, connective tissue growth factor (CTGF), which is involved in TGF-b, BMP and Wnt signaling, was upregulated in both stromal and LSK cells in the first day of co-culture. To study a possible extrinsic role of CTGF as a stromal mediator, we co-cultured siCTGF knockdown stromal cells with wild-type LSK cells. Since self-renewal requires cell division, we focused on cell cycle regulation of LSK cells. We found that knockdown of CTGF in stromal cells downregulates CTGF in LSK cells. In addition, knockdown of stromal CTGF downregulated Ccnd1, Cdk2, Cdkn1a (p21), Ep300 and Fos. On the other hand, decreased CTGF in stromal cells upregulates Cdkn1b (p27) and phosphorylation of Smad2/3. These results show that stromal CTGF regulates the cell cycle of LSK cells. On a functional level, we found that decreased stromal CTGF results in an increased production of MPP and myeloid colony-forming cells in 1-week co-cultures. We will present data showing whether and how a decrease in CTGF in stromal cells affects the maintenance of transplantable HSC. In summary, our current results indicate that reduced expression of CTGF in stromal cells regulates mediators of cell cycle and Smad2/3-mediated signaling in LSK cells, resulting in an increased production of myeloid progenitors. Disclosures: No relevant conflicts of interest to declare.

Discovery of embryonic stem cells and the concept of regenerative medicine

2010 ◽  
pp. 189-192
Author(s):  
Martin J. Evans
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Regenerative Medicine ◽  
Nobel Prize ◽  
Embryonic Stem ◽  
Differentiated Cells ◽  
Teratocarcinoma Cells ◽  
Mammalian Embryos ◽  
Development Proceeds ◽  
Fertilized Egg

In this chapter Sir Martin Evans, who was awarded the Nobel Prize for Physiology or Medicine in 2007, describes the identification of stem cells, initially from certain cultured tumour cells (teratocarcinoma cells) and latterly from early mammalian embryos. The differentiated cells of the adult vertebrate arise from a single fertilized egg and as development proceeds the commitment to differentiation becomes irreversible....

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