Simple insoluble cues specify stem cell differentiation

Dingal, P.C. Dave P.; Wells, Rebecca G.; Discher, Dennis E.

doi:10.1073/pnas.1421562112

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…Instead, there is a close association between TGFβRII and non‐canonical Akt levels, which could explain the Smad results since Akt prevents phosphorylation of Smad3 and dampens activation of the Smad pathway. [ 22,69 ] Moreover, these results offer an interesting prospect for a multi‐factored manipulation of tissue engineered constructs, where the change of a single design parameter of the bioengineered microenvironment can program different cellular responses.…”

Section: Resultsmentioning

confidence: 99%

“…[20] Additionally, it has also become increasingly evident that the synergy between structural and soluble cues is essential for an effective recreation of lineage differentiation steps. [22][23][24][25] Following this rationale, several recent studies have demonstrated the potential of composite systems capable of simultaneously modulating both types of stimuli by providing a controlled release of specific bioactive molecules like growth factors (GFs). [26][27][28][29] However, the use of exogenous biomolecules in these systems also presents several intrinsic limitations, such as their extremely-short halflives, requiring the use of high doses to obtain relevant biological effects.…”

Section: Introductionmentioning

confidence: 99%

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Guiding Stem Cell Tenogenesis by Modulation of Growth Factor Signaling and Cell‐Scale Biophysical Cues in Bioengineered Constructs

Teixeira,

Pardo,

Bakht

et al. 2024

Adv Funct Materials

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Tendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)‐β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis‐inductive constructs. MINPs are first solid phase‐imprinted against a TGF‐β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically‐responsive microfibers are then encapsulated together with adipose‐derived stem cells within gelatin‐based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF‐β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF‐β signaling, which promotes the expression of tendon‐associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Guiding Stem Cell Tenogenesis by Modulation of Growth Factor Signaling and Cell‐Scale Biophysical Cues in Bioengineered Constructs

Teixeira,

Pardo,

Bakht

et al. 2024

Adv Funct Materials

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show abstract

“…The gene expression levels of an hMSC are known to be the decisive regulators of hMSCs differentiation. These gene expression levels might be influenced by both cell internal cues (De-Leon and Davidson, 2007;Ralston, 2008) and external cues (Engler et al, 2006;Eyckmans et al, 2012;Hess et al, 2012a;Dingal et al, 2014;Najafabadi et al, 2016). Experimental studies (Mousavi and Hamdy Doweidar, 2015) have shown that the in vitro differentiation of hMSC into cells of distinct functional types can be controlled by external factors.…”

Section: Introductionmentioning

confidence: 99%

A General Theoretical Framework to Study the Influence of Electrical Fields on Mesenchymal Stem Cells

Dawson

Lee

Rienen

et al. 2020

Front. Bioeng. Biotechnol.

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Mesenchymal stem cell dynamics involve cell proliferation and cell differentiation into cells of distinct functional type, such as osteoblasts, adipocytes, or chondrocytes. Electrically active implants influence these dynamics for the regeneration of the cells in damaged tissues. How applied electric field influences processes of individual stem cells is a problem mostly unaddressed. The mathematical approaches to study stem cell dynamics have focused on the stem cell population as a whole, without resolving individual cells and intracellular processes. In this paper, we present a theoretical framework to describe the dynamics of a population of stem cells, taking into account the processes of the individual cells. We study the influence of the applied electric field on the cellular processes. We test our mean-field theory with the experiments from the literature, involving in vitro electrical stimulation of stem cells. We show that a simple model can quantitatively describe the experimentally observed time-course behavior of the total number of cells and the total alkaline phosphate activity in a population of mesenchymal stem cells. Our results show that the stem cell differentiation rate is dependent on the applied electrical field, confirming published experimental findings. Moreover, our analysis supports the cell density-dependent proliferation rate. Since the experimental results are averaged over many cells, our theoretical framework presents a robust and sensitive method for determining the effect of applied electric fields at the scale of the individual cell. These results indicate that the electric field stimulation may be effective in promoting bone regeneration by accelerating osteogenic differentiation.

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“…The gene expression levels of an hMSC are known to be the decisive regulators of hMSCs differentiation. These gene expression levels might be influenced by both cell internal cues [De-Leon and Davidson (2007); Ralston (2008)] and external cues [Eyckmans et al (2012); Najafabadi et al (2016); Dingal et al (2014); Eng (2006); Hess et al (2012b)]. Experimental studies [Mousavi and Hamdy Doweidar (2015)] have shown that the in vitro differentiation of hMSC into cells of distinct functional types can be controlled by external factors.…”

Section: Introductionmentioning

confidence: 99%

A theoretical framework to study the influence of electrical fields on mesenchymal stem cells

Dawson

Lee

Rienen

et al. 2020

Preprint

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2Mesenchymal stem cell dynamics involves cell proliferation and cell differentiation into cells 3 of distinct functional type, such as osteoblasts, adipocytes, or chondrocytes. Electrically 4 active implants influence these dynamics for the regeneration of the cells in damaged tissues. 5 How applied electric field influences processes of individual stem cells is a problem mostly 6 unaddressed. The mathematical approaches to study stem cell dynamics have focused on the 7 stem cell population as a whole, without resolving individual cells and intracellular processes. 8 In this paper, we present a theoretical framework to describe the dynamics of a population of 9 stem cells, taking into account the processes of the individual cells. We study the influence 10 of the applied electric field on the cellular processes. We test our mean-field theory with the 11 experiments from the literature, involving in vitro electrical stimulation of stem cells. We show that 12 a simple model can quantitatively describe the experimentally observed time-course behavior of 13 the total number of cells and the total alkaline phosphate activity in a population of mesenchymal 14 stem cells. Our results show that the stem cell differentiation rate is dependent on the applied 15 electrical field, confirming published experimental findings. Moreover, our analysis supports the 16 cell density-dependent proliferation rate. Since the experimental results are averaged over many 17 cells, our theoretical framework presents a robust and sensitive method for determining the effect 18 of applied electric fields at the scale of the individual cell. These results indicate that the electric 19 field stimulation may be effective in promoting bone regeneration by accelerating osteogenic 20 differentiation. 21 Human mesenchymal stem cells (hMSCs) possess a unique capability of self-renewal and differentiation 23 into cells of various types of tissues, such as bone, cartilage, and adipose. Thus the hMSCs are the promising 24 cell types for regenerative medicine and tissue engineering. The gene expression levels of an hMSC are 25 known to be the decisive regulators of hMSCs differentiation. These gene expression levels might be 26 influenced by both cell internal cues [De-Leon and Davidson (2007); Ralston (2008)] and external cues Experimental studies [Mousavi and Hamdy Doweidar (2015)] have shown that the in vitro differentiation 29 of hMSC into cells of distinct functional types can be controlled by external factors. Therefore, stem cell 30 differentiation mediated by external factors is a compelling approach that has led to the development of 31 bio-implants, for clinical applications in regenerative medicine. 32The applied electric field (EF) is one of the proven external factors known to influence hMSCs dynamics 33 such as migration [Funk (2015); Banks et al. (2015); Ciombor and Aaron (1993); Schemitsch and Kuzyk 34 (2009)], elongation [Rajnicek et al. (2008); Tandon et al. (2009)], proliferation [Sun et al. (2009); Hartig 35 et al. (2000); Ki...

show abstract

Simple insoluble cues specify stem cell differentiation

Cited by 9 publications

References 23 publications

Guiding Stem Cell Tenogenesis by Modulation of Growth Factor Signaling and Cell‐Scale Biophysical Cues in Bioengineered Constructs

Guiding Stem Cell Tenogenesis by Modulation of Growth Factor Signaling and Cell‐Scale Biophysical Cues in Bioengineered Constructs

A General Theoretical Framework to Study the Influence of Electrical Fields on Mesenchymal Stem Cells

A theoretical framework to study the influence of electrical fields on mesenchymal stem cells

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