Ancestral Background Is Underreported in Regenerative Engineering

Ryan, Holly; Bister, Daniel; Holliday, Sophia A.; Boehlein, Jessica; Lewis, Aljae; Silberman, Justin; Allen, Josephine B.; Moore, Erika

doi:10.1007/s40883-021-00237-8

Cited by 14 publications

(4 citation statements)

References 11 publications

(14 reference statements)

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“…Patient-derived organoids are also an opportunity to better understand sex- and ancestry-driven differences in TME dynamics, which has thus far not been addressed. Given the emerging information on sex- and ancestry-driven differences in cell sourcing and disease [ 103 – 105 ], this is a critical gap in matrisome knowledge. Yet, organoids do not often sustain/include stromal cells and thus their TME remains limited.…”

Section: Experimentally Modeling the Dynamic Tmementioning

confidence: 99%

Challenges and Opportunities Modeling the Dynamic Tumor Matrisome

2023

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We need novel strategies to target the complexity of cancer and, particularly, of metastatic disease. As an example of this complexity, certain tissues are particularly hospitable environments for metastases, whereas others do not contain fertile microenvironments to support cancer cell growth. Continuing evidence that the extracellular matrix (ECM) of tissues is one of a host of factors necessary to support cancer cell growth at both primary and secondary tissue sites is emerging. Research on cancer metastasis has largely been focused on the molecular adaptations of tumor cells in various cytokine and growth factor environments on 2-dimensional tissue culture polystyrene plates. Intravital imaging, conversely, has transformed our ability to watch, in real time, tumor cell invasion, intravasation, extravasation, and growth. Because the interstitial ECM that supports all cells in the tumor microenvironment changes over time scales outside the possible window of typical intravital imaging, bioengineers are continuously developing both simple and sophisticated in vitro controlled environments to study tumor (and other) cell interactions with this matrix. In this perspective, we focus on the cellular unit responsible for upholding the pathologic homeostasis of tumor-bearing organs, cancer-associated fibroblasts (CAFs), and their self-generated ECM. The latter, together with tumoral and other cell secreted factors, constitute the “tumor matrisome”. We share the challenges and opportunities for modeling this dynamic CAF/ECM unit, the tools and techniques available, and how the tumor matrisome is remodeled (e.g., via ECM proteases). We posit that increasing information on tumor matrisome dynamics may lead the field to alternative strategies for personalized medicine outside genomics.

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Section: Experimentally Modeling the Dynamic Tmementioning

confidence: 99%

Challenges and Opportunities Modeling the Dynamic Tumor Matrisome

2023

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“…This overt lack of inclusivity exacerbates disparity in treatment outcomes. A recent article surveyed the biomedical research landscape in regenerative engineering to conclude that ancestral background was significantly under-reported in preclinical in vitro studies ( Ryan et al, 2021 ). We aim to show here that the under-representation of ethnically diverse enrollees in clinical cancer trials ( Aldrighetti et al, 2021 ) can in part be improved with expansive and inclusive preclinical cancer research.…”

Section: Powerful Opportunities In Preclinical Cancer Modelsmentioning

confidence: 99%

How inclusive are cell lines in preclinical engineered cancer models?

Raghavan

2022

Disease Models &Amp; Mechanisms

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Diverse factors contribute to significant and dire disparities in cancer risk and treatment outcomes. To address this, there was a call for inclusion of sex as a biological variable, which resulted in more instances of careful inclusion of sex in preclinical studies of cancer. Another variable in cancer treatment is genetic ancestry. Although this is considered explicitly in clinical research, it is considerably neglected in preclinical studies. Preclinical research can use several 3D in vitro model systems, such as spheroids/organoids, xenografts, or other bioengineered systems that combine biomaterials and cellular material. Ultimately, the cellular base for all of these in vitro model systems is derived from human cell lines or patient samples, to investigate mechanisms of cancer and screen novel therapeutics, all of which aim to maximize successful outcomes in clinical trials. This in itself offers an opportunity to potentiate effective treatments for many groups of people, when diverse variables like genetic ancestry are consciously included into study design. This Perspective highlights the need for conscious inclusion of genetic ancestry in preclinical cancer tissue engineering, especially when it pertains to determining therapeutic outcomes.

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“…Tissue engineering approaches often rely on cells of unknown origin or that lack diversity related to sex, age, and ethnicity [14, 15]. Indeed, bone healing can be influenced by many factors including pre-existing health conditions, age, and sex.…”

Section: Introductionmentioning

confidence: 99%

Donor Variability in Human Mesenchymal Stem Cell Osteogenic Response as a Function of Passage Conditions and Donor Sex

Kolliopoulos,

Tiffany,

Polanek

et al. 2023

Preprint

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Contemporary tissue engineering efforts often seek to use mesenchymal stem cells (MSCs) due to their potential to differentiate to various tissue-specific cells and generate a pro-regenerative secretome. While MSC differentiation and therapeutic potential can differ as a function of matrix environment, it may also be widely influenced as a function of donor-to-donor variability. Further, effects of passage number and donor sex may further convolute the identification of clinically effective MSC-mediated regeneration technologies. We report efforts to adapt a well-defined mineralized collagen scaffold platform to study the influence of MSC proliferation and osteogenic potential as a function of passage number and donor sex. Mineralized collagen scaffolds broadly support MSC osteogenic differentiation and regenerative potency in the absence of traditional osteogenic supplements for a wide range of MSCs (rabbit, rat, porcine, human). We obtained a library of bone marrow and adipose tissue derived stem cells to examine donor-variability of regenerative potency in mineralized collagen scaffolds. MSCs displayed reduced proliferative capacity as a function of passage duration. Further, MSCs showed significant sex-based differences. Notably, MSCs from male donors displayed significantly higher metabolic activity and proliferation while MSCs from female donor displayed significantly higher osteogenic response via increased alkaline phosphate activity, osteoprotegerin release, and mineral formation in vitro. Our study highlights the essentiality of considering MSC donor sex and culture expansion in future studies of biomaterial regenerative potential.

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Ancestral Background Is Underreported in Regenerative Engineering

Cited by 14 publications

References 11 publications

Challenges and Opportunities Modeling the Dynamic Tumor Matrisome

Challenges and Opportunities Modeling the Dynamic Tumor Matrisome

How inclusive are cell lines in preclinical engineered cancer models?

Donor Variability in Human Mesenchymal Stem Cell Osteogenic Response as a Function of Passage Conditions and Donor Sex

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