&lt;u&gt;S&lt;/u&gt;tart &lt;u&gt;l&lt;/u&gt;ate or &lt;u&gt;f&lt;/u&gt;inish &lt;u&gt;e&lt;/u&gt;arly

Song, Shuang; Liu, Xu; Wu, Qinzhe; Gerstlauer, Andreas; Li, Tao; John, Lizy K.

doi:10.14778/3282495.3282501

Cited by 24 publications

(6 citation statements)

References 46 publications

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“…At 24 weeks gestation, from a volume of amniotic fluid of approximately 600 ml surrounding the fetus [32], a 10-ml aliquot obtained by amniocentesis avoids the inherent risk of hemorrhage, preterm labor, and fetal demise associated with a fetal skin or placenta biopsy [7]. An amniocentesis also has virtually no added morbidity because it is often a recommended test conducted in the prenatal workup of a major cardiac anomaly to rule out an abnormal karyotype [33]. Furthermore, our group, among others [34], has previously shown that amniotic fluid cells can be harvested without maternal cell contamination and are therefore derived exclusively from the fetus [10].…”

Section: Discussionmentioning

confidence: 99%

Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells

Jiang

Herron

Bernardo

et al. 2016

Stem Cells Translational Medicine

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The establishment of an abundant source of autologous cardiac progenitor cells would represent a major advance toward eventual clinical translation of regenerative medicine strategies in children with prenatally diagnosed congenital heart disease. In support of this concept, we sought to examine whether functional, transgene-free human cardiomyocytes (CMs) with potential for patient-specific and autologous applications could be reliably generated following routine amniocentesis. Under institutional review board approval, amniotic fluid specimens (8-10 ml) at 20 weeks gestation were expanded and reprogrammed toward pluripotency using nonintegrating Sendai virus (SeV) expressing OCT4, SOX2, cMYC, and KLF4. Following exposure of these induced pluripotent stem cells to cardiogenic differentiation conditions, spontaneously beating amniotic fluid-derived cardiomyocytes (AF-CMs) were successfully generated with high efficiency. After 6 weeks, quantitative gene expression revealed a mixed population of differentiated atrial, ventricular, and nodal AF-CMs, as demonstrated by upregulation of multiple cardiac markers, including MYH6, MYL7, TNNT2, TTN, and HCN4, which were comparable to levels expressed by neonatal dermal fibroblast-derived CM controls. AF-CMs had a normal karyotype and demonstrated loss of NANOG, OCT4, and the SeV transgene. Functional characterization of SIRPA + AF-CMs showed a higher spontaneous beat frequency in comparison with dermal fibroblast controls but revealed normal calcium transients and appropriate chronotropic responses after b-adrenergic agonist stimulation. Taken together, these data suggest that somatic cells present within human amniotic fluid can be used to generate a highly scalable source of functional, transgene-free, autologous CMs before a child is born. This approach may be ideally suited for patients with prenatally diagnosed cardiac anomalies. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1595-1606 SIGNIFICANCEThis study presents transgene-free human amniotic fluid-derived cardiomyocytes (AF-CMs) for potential therapy in tissue engineering and regenerative medicine applications. Using 8-10 ml of amniotic fluid harvested at 20 weeks gestation from normal pregnancies, a mixed population of atrial, ventricular, and nodal AF-CMs were reliably generated after Sendai virus reprogramming toward pluripotency. Functional characterization of purified populations of beating AF-CMs revealed normal calcium transients and appropriate chronotropic responses after b-adrenergic agonist stimulation in comparison with dermal fibroblast controls. Because AF-CMs can be generated in fewer than 16 weeks, this approach may be ideally suited for eventual clinical translation at birth in children with prenatally diagnosed cardiac anomalies.

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Section: Discussionmentioning

confidence: 99%

Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells

Jiang

Herron

Bernardo

et al. 2016

Stem Cells Translational Medicine

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“…For the collagen-only ECM, treatment with each of the CXCL12 isoforms resulted in multicellular extensions or sprouts from the endothelial layer at the vessel/ECM interface ( Figure 3A). In contrast, for the collagen/HA ECM, treatment with the individual CXCL12 isoforms promoted sheet-like migration of the endothelial cells that was reminiscent of local vessel dilation [31] ( Figure 3B). We further characterized this vessel dilation response by analyzing the total area displacement of the HUVEC monolayer into the collagen/HA ECM during the course of the experiments ( Figure S1, Supporting Information).…”

Section: Sprouting Angiogenesis Mediated By Cxcl12 Isoforms Is Continmentioning

confidence: 98%

Distinguishing Specific CXCL12 Isoforms on Their Angiogenesis and Vascular Permeability Promoting Properties

Chang

Seibel

Avendano

et al. 2020

Adv Healthcare Materials

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Angiogenesis is associated with increased vessel sprouting and permeability. Important mediators of these angiogenic responses include local environment of signaling molecules and supporting extracellular matrix (ECM). However, dissecting the interplay of these instructive signals in vivo with multiple cells and extracellular molecules remains a central challenge. Here, microfluidic biomimicry is integrated with 3D ECM hydrogels that are well‐characterized for molecular‐binding and mechanical properties to reconstitute vessel‐like analogues in vitro. This study focuses on three distinct isoforms of the pro‐metastatic chemokine CXCL12. In collagen‐only hydrogel, CXCL12‐α is the most potent isoform in promoting sprouting and permeability, followed by CXCL12‐β and CXCL12‐γ. Strikingly, addition of hyaluronan (HA), a large and negatively charged glycosaminoglycan, with collagen matrices selectively increases vessel sprouting and permeability conferred by CXCL12‐γ. This outcome is supported by the measured binding affinities to collagen/HA ECM, suggesting that negatively charged HA increases the binding of CXCL12‐γ to augment its angiogenic potency. Moreover, it is shown that addition of HA to collagen matrices on its own decreases vessel sprouting and permeability, and these responses are nullified by blocking the HA receptor CD44. Collectively, these results demonstrate that differences in binding to extracellular HA help underlie CXCL12 isoform‐specific responses toward directing angiogenesis.

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“…In negative VEGF gradients, a process resembles vessel dilation occurred as the ECs spread into a sheet-like formation. [82] These studies show that the dosage, gradient profile, and timing of the addition of the growth factors all affect the outcome of the tissue vascularization in vitro.…”

Section: Chemical Factor: Growth Factorsmentioning

confidence: 96%

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

Tan

Leung

2020

Small

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Vascularization of engineered tissue constructs remains one of the greatest unmet challenges to mimicking the native tissue microenvironment in vitro. The main obstacle is recapitulating the complexity of the physiological environment while providing simplicity in operation and manipulation of the model. Microfluidic technology has emerged as a promising tool that enables perfusion of the tissue constructs through engineered vasculatures and precise control of the vascular microenvironment cues in vitro. The tunable microenvironment includes i) biochemical cues such as coculture, supporting matrix, and growth factors and ii) engineering aspects such as vasculature engineering methods, fluid flow, and shear stress. In this systematic review, the design considerations of the microfluidic‐based in vitro model are discussed, with an emphasis on microenvironment control to enhance the development of next‐generation vascularized engineered tissues.

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<u>S</u>tart <u>l</u>ate or <u>f</u>inish <u>e</u>arly

Cited by 24 publications

References 46 publications

Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells

Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells

Distinguishing Specific CXCL12 Isoforms on Their Angiogenesis and Vascular Permeability Promoting Properties

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

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