Scalable Cardiac Differentiation of Pluripotent Stem Cells Using Specific Growth Factors and Small Molecules

2017 ◽  
pp. 39-69 ◽  
Author(s):  
Henning Kempf ◽  
Robert Zweigerdt
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Small Molecules ◽  
Pluripotent Stem Cells ◽  
Specific Growth ◽  
Cardiac Differentiation

scholarly journals Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy

2021 ◽  
Author(s):  
Tingcai Pan ◽  
Ning Wang ◽  
Jiaye Zhang ◽  
Fan Yang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Small Molecules ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Cost Effective ◽  
Human Pluripotent Stem Cells ◽  
Scale Production ◽  
Hepatic Cells ◽  
Cell Based Therapy

Abstract Background: Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable. Methods: We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.Results: We demonstrated that small-molecule cocktail CIP efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo. Conclusion: Our current small-molecule based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.

scholarly journals Migration of mouse-induced pluripotent stem cells to glioma-conditioned medium is mediated by tumor-associated specific growth factors

2011 ◽  
Vol 2 (2) ◽  
pp. 283-288 ◽  
Author(s):  
SHINICHIRO KOIZUMI ◽  
CHUNYU GU ◽  
SHINJI AMANO ◽  
SEIJI YAMAMOTO ◽  
HAYATO IHARA ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Induced Pluripotent Stem Cells ◽  
Conditioned Medium ◽  
Pluripotent Stem Cells ◽  
Specific Growth ◽  
Induced Pluripotent

Abstract 6: Formation of Human Heart Muscle Directly from Embryonic and Induced Pluripotent Stem Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
James E Hudson ◽  
Malte Tiburcy ◽  
Wolfram-Hubertus Zimmermann
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Stromal Cells ◽  
Pluripotent Stem Cells ◽  
Heart Muscle ◽  
Human Heart ◽  
Cardiac Differentiation ◽  
Mechanical Stimuli ◽  
Serum Free ◽  
Electrical Pacing

Tissue engineering enables the simulation of human heart physiology and pathology. It typically requires a mixture of cardiomyocytes, stromal cells, and extracellular matrix for fabrication. Here, we hypothesised that bioengineered heart muscle (BHM) can be formed directly from undifferentiated pluripotent stem cells by triggering processes of embryonic cardiogenesis. Methods and Results: We tested our hypothesis by applying an optimized serum-free cardiac differentiation protocol to undifferentiated pluripotent stem cells in a collagen type 1 hydrogel. During this process BHMs traversed through distinct developmental stages: early mesoderm (3 days), cardiac specification (10 days), and cardiac maturation (up to 50 days). Flow cytometry demonstrated that BHMs are comprised of primarily cardiomyocytes (α-actinin positive cells, 51 ± 5%, n = 6) and stromal cells (CD90 positive cells, 41 ± 5%, n = 6), with low yields of contaminating cells. By 22 days the BHMs exhibited measurable contractile force (207 ± 19 μN) and contained elongated cross-striated cardiomyocytes. We next sought to optimize the force of contraction and also the maturity of the BHM, by investigating the effect of mechanical stimuli and growth factors. Mechanical stimulation was essential for BHM formation. Additionally, we found that 2 developmentally important growth factors, FGF2 and TGFβ1, induced pathological and physiological hypertrophy, respectively. This was characterized by an increase in cell size in both conditions coupled with reduced force and higher ANP expression in FGF2 treated BHM, and a higher force with reduced ANP expression and elevated β-MHC/α-MHC ratio TGFβ1 treated BHM. Using our optimized protocol, 28 day old BHM responded to electrical pacing, preloading, and inotropic stimuli similarly as bona fide myocardium. Conclusion: BHM can be formed directly with undifferentiated pluripotent stem cells by recapitulating normal cardiac development. The serum-free protocol with developmentally defined stimuli provides us with a useful in vitro model to study cardiac biology and potentially provides a method of producing cardiac tissue for regenerative applications.

scholarly journals Controlled Release of Small Molecules for Cardiac Differentiation of Pluripotent Stem Cells

2018 ◽  
Vol 24 (23-24) ◽  
pp. 1798-1807 ◽  
Author(s):  
Christopher J. Tsao ◽  
Francesca Taraballi ◽  
Laura Pandolfi ◽  
Aaron J. Velasquez-Mao ◽  
Rodrigo Ruano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Controlled Release ◽  
Small Molecules ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation

Isolation, Characterization, and Differentiation of Stem Cells From Various Dental Sources: An In Vitro Study

2021 ◽  
pp. 232020682110107
Author(s):  
Sandeep S. Katti ◽  
Kishore Bhat ◽  
Chetana Bogar
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Statistical Analysis ◽  
Specific Growth ◽  
Culture Media ◽  
In Vitro Study ◽  
Central Research ◽  
Cell Lineages ◽  
Apical Papilla

Aim: The aim of the current study was to isolate stem cells from various dental sources such as dental pulp, periodontal ligament (PDL), and apical papilla, and to characterize stem cells by staining for the presence/absence of specific surface markers and also to differentiate stem cells into osteogenic, chondrogenic, and adipogenic cell lineages by exposing them to specific growth factors under the ideal conditions. Materials and Methods: A total of 117 samples were included in the study, consisting of 30 pulp, 50 gingival, 35 PDL, and 2 apical papilla samples. The pulp was extirpated and transported to the Central Research Laboratory. Gingival connective tissue was collected from the participants undergoing any crown lengthening procedure or any gingivectomy procedure from the Department of Periodontology. A similar procedure was also followed for apical papilla and PDL. Isolation was done followed by the identification of the cells by immunocytochemistry using different markers. Once the identity of cells was confirmed, these cells were treated with different culture media to attain 70% to 100% confluency. Then the medium was replaced with a conditioning medium containing specific growth factors for differentiation into osteogenic, chondrogenic, and adipogenic cell lineages. Result: In our study, the number of samples collected and processed was 117. The isolation rate of stem cells from the above-collected samples was 70%. Statistical analysis—no statistical analysis was done as there was no variability expected. Conclusion: Our study showed that stem cells could be isolated, differentiated, and characterized from different dental sources.

In vitro propagation and cardiac differentiation of canine induced pluripotent stem cells on carbon nanotube substrates

2021 ◽  
pp. 101571
Author(s):  
Mahalakshmi Natarajan ◽  
Purnima Singh ◽  
Tanmay Mondal ◽  
Kuldeep Kumar ◽  
Kinsuk Das ◽  
...  
Keyword(s):  
Stem Cells ◽  
Carbon Nanotube ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
In Vitro Propagation ◽  
Cardiac Differentiation ◽  
Induced Pluripotent

scholarly journals 422Enrichment of cardiac differentiation of mouse pluripotent stem cells by beta 3 adrenoceptor stimulation

2018 ◽  
Vol 114 (suppl_1) ◽  
pp. S103-S103
Author(s):  
V Spinelli ◽  
L Sartiani ◽  
A Laurino ◽  
L Raimondi ◽  
M Calvani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation

Growth Factors and the Serum-Free Culture of Human Pluripotent Stem Cells

2013 ◽  
pp. 357-363
Author(s):  
Alice Pébay ◽  
Martin F. Pera
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Serum Free

scholarly journals Rabbit induced pluripotent stem cells retain capability of in vitro cardiac differentiation

2019 ◽  
Vol 68 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Praopilas Phakdeedindan ◽  
Piyathip Setthawong ◽  
Narong Tiptanavattana ◽  
Sasitorn Rungarunlert ◽  
Praewphan Ingrungruanglert ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Induced Pluripotent
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