James Ankrum

James Ankrum
University of Iowa | UI · Roy J. Carver Department of Biomedical Engineering

BSE, MPhil, PhD

About

99
Publications
56,399
Reads
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5,241
Citations
Introduction
My lab focuses on developing platform technologies to control the phenotype of transplanted cells. Of particular interest are engineered mesenchymal stem cell therapies to treat inflammatory conditions and engineered pancreatic beta cell therapies for treatment of type 1 diabetes.
Additional affiliations
January 2023 - present
Royal College of Surgeons in Ireland
Position
  • Visiting Professor
Description
  • Fulbright Scholar working in the Tissue Engineering Research Group led by Prof. Fergal O'Brien on scaffold design for wound healing.
January 2015 - present
University of Iowa
Position
  • Professor (Assistant)
Description
  • Cell Biology for Engineers, Senior Design I & II
August 2014 - present
University of Iowa
Position
  • PI
Education
September 2008
Massachusetts Institute of Technology
Field of study
  • Medical Engineering & Medical Physics
September 2007 - August 2008
University of Cambridge
Field of study
  • Engineering Design
August 2003 - May 2007
University of Iowa
Field of study
  • Biomedical Engineering

Publications

Publications (99)
Article
Full-text available
Cell therapies enable unprecedented treatment options to replace tissues, destroy tumors and facilitate regeneration. The greatest challenge facing cell therapy is the inability to control the fate and function of cells after transplantation. We have developed an approach to control cell phenotype in vitro and after transplantation by engineering c...
Article
Full-text available
The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or 'immune privileged'; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-...
Article
Full-text available
The ability to use mesenchymal stromal cells (MSC) directly out of cryostorage would significantly reduce the logistics of MSC therapy by allowing on-site cryostorage of therapeutic doses of MSC at hospitals and clinics. Such a paradigm would be especially advantageous for the treatment of acute conditions such as stroke and myocardial infarction,...
Article
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Background Immunomodulation by mesenchymal stromal cells (MSCs) can occur through trophic factor mechanisms, however, intravenously infused MSCs are rapidly cleared from the body yet a potent immunotherapeutic response is still observed. Recent work suggests that monocytes contribute to the clearance of MSCs via efferocytosis, the body’s natural me...
Article
Full-text available
Polychlorinated biphenyl (PCB) accumulates in adipose where it may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein, we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC)...
Preprint
Knockdown (KD) of lipid droplet (LD) protein perilipin 2 (PLIN2) in beta cells impairs glucose-stimulated insulin secretion (GSIS) and mitochondrial function. Here, we addressed a pathway responsible for compromised mitochondrial integrity in PLIN2 KD beta cells. In PLIN2 KD human islets, mitochondria were fragmented in beta cells but not in alpha...
Article
Scarring from traumatic injury, burns, and other complications remains a significant problem that diminishes quality of life for millions of people worldwide. A common target for the development of new therapies to promote healing and reduce scarring are myofibroblasts because of their central role in pathological scarring. Recent work indicates th...
Article
Full-text available
Ex vivo follicle growth is an essential tool, enabling interrogation of folliculogenesis, ovulation, and luteinization. Though significant advancements have been made, existing follicle culture strategies can be technically challenging and laborious. In this study, we advanced the field through development of a custom agarose micromold, which enabl...
Article
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Adipose tissue plays a crucial role in metabolic syndrome, autoimmune diseases, and many cancers. Because of adipose’s role in so many aspects of human health, there is a critical need for in vitro models that replicate adipose architecture and function. Traditional monolayer models, despite their convenience, are limited, showing heterogeneity and...
Article
Context Obesity is a disease with deleterious effects on the female reproductive tract, including the endometrium. Objective We sought to understand the effects of excess adipose on the benign endometrium. Methods A physiologic in vitro coculture system was developed, consisting of multicellular human endometrial organoids, adipose spheroids, and...
Article
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Polychlorinated biphenyls (PCBs) were used extensively in building materials, including those used in schools. PCBs accumulate in fat, and exposure to PCBs is associated with the development of cancer, neurodevelopmental disorders, cardiovascular disease, obesity, and diabetes. The non-dioxin-like PCB congener, PCB52 (2,2',5,5'-tetrachlorobiphenyl)...
Article
Full-text available
Introduction With technical advances, confocal and super-resolution microscopy have become powerful tools to dissect cellular pathophysiology. Cell attachment to glass surfaces compatible with advanced imaging is critical prerequisite but remains a considerable challenge for human beta cells. Recently, Phelps et al. reported that human beta cells p...
Article
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Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a three-dimensional human adipocyte spheroid system that has an adipokine profile similar to in vivo adipose...
Article
Polychlorinated biphenyls (PCBs) accumulate in adipose tissue and are linked to obesity and diabetes. The congener, PCB52 (2,2',5,5'-tetrachorobiphenyl), is found at high levels in school air. Hydroxylation of PCB52 to 4-OH-PCB52 (4-hydroxy-2,2',5,5'-tetrachorobiphenyl) may increase its toxicity. To understand PCB52's role in causing adipose dysfun...
Preprint
Full-text available
Adipocytes regulate tissues through production of adipokines that can act both locally and systemically. Adipocytes also have been found to play a critical role in regulating the healing process. To better understand this role, we developed a 3D human adipocyte spheroid system that has an adipokine profile similar to in vivo adipose tissues. Previo...
Preprint
Full-text available
PCBs accumulate in adipose where they may impact the growth and function of cells within the tissue. This is particularly concerning during adolescence when adipocytes expand rapidly. Herein we sought to understand how exposure to PCB mixtures found in U.S. schools affects human adipose mesenchymal stem/stromal cell (MSC) health and function. We in...
Article
Full-text available
Exposure to polychlorinated biphenyls (PCBs) has been associated with the development of metabolic syndrome, a cluster of diseases that includes obesity, diabetes, liver steatosis, and cardiovascular problems. PCBs accumulate and fat and are known to act on adipocytes and their precursors, termed preadipocytes. The PCB congener, PCB126, has been sh...
Article
Full-text available
Mesenchymal stromal cell (MSC) therapy has seen increased attention as a possible option to treat a number of inflammatory conditions including COVID-19 acute respiratory distress syndrome (ARDS). As rates of obesity and metabolic disease continue to rise worldwide, increasing proportions of patients treated with MSC therapy will be living with obe...
Article
Lipid droplets (LDs) , organelles important for intracellular lipid metabolism, are actively formed in rat and human adult beta cells and affect islet function and health. Acute mobilization of LDs by adipose triglyceride lipase in beta cells is known to support insulin secretion. As LD degradation by lysosomal acid lipase (LIPA) through lipophagy...
Article
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that accumulate in adipose tissue and have been associated with cardiometabolic disease. We have previously demonstrated that exposure of human preadipocytes to the dioxin-like PCB126 disrupts adipogenesis via the aryl hydrocarbon receptor (AhR). To further understand how PCB126 dis...
Article
Full-text available
The number of mesenchymal stromal/stem cell (MSC) therapeutics and types of clinical applications have greatly diversified during the past decade, including rapid growth of poorly regulated “Stem Cell Clinics” offering diverse “Unproven Stem Cell Interventions.” This product diversification necessitates a critical evaluation of the reliance on the...
Article
Coating mesenchymal stromal cells with a soft gel incorporating specific chemomechanical cues that enhance the production of collagenases enhances the ability of the cells to inhibit aberrant tissue remodelling in mice with fibrotic lungs.
Article
Full-text available
Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet...
Article
Coupling a photosensitizer to camptothecin enhances selectivity and potency of the chemotherapy to kill cancer cells in vitro and in vivo.
Article
An automated decision support tool could expand access to intensive insulin therapy for patients with type 1 diabetes.
Preprint
Full-text available
Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in β cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects β cell function under nutritional stress, PLIN2 was down-regulated in mouse β cells, INS1 cells, and human islet...
Article
Optimizing nanoparticle size, charge, and route of delivery enables highly efficient and selective targeting of tumor-associated macrophages.
Article
Full-text available
Aryl hydrocarbon receptor (AHR) agonists such as dioxin have been associated with obesity and the development of diabetes. Whole-body Ahr knockout mice on high-fat diet (HFD) have been shown to resist obesity and hepatic steatosis. Tissue-specific knockout of Ahr in mature adipocytes via adiponectin-Cre exacerbates obesity while knockout in liver i...
Article
Full-text available
Purpose: The purpose of this study was to determine mesenchymal stem cell (MSC) therapy efficacy on rescuing the visual system in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS) and to provide new mechanistic insights. Methods: EAE was induced in female C57BL6 mice by immunization with myelin oligodendrocyte...
Article
Full-text available
Adipocytes and adipose tissue derived cells have been investigated for their potential to contribute to the wound healing process. However, the details of how these cells interact with other essential cell types, such as myofibroblasts/fibroblasts, remain unclear. Using a novel in-vitro 3D human adipocyte/pre-adipocyte spheroid model, we investigat...
Article
Full-text available
Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory p...
Article
Deep learning outperforms general practitioners in diagnosing 26 common skin conditions.
Article
Background & Aim MSC immunomodulation has been central to the expanded use of MSCs within clinical trials. Inflammatory cytokine licensing of an anti-inflammatory MSC phenotype has emerged as a promising driver of enhanced MSC immunosuppressive capacity, however, the mechanism(s) that facilitate this enhancement, as well as critical modifiers of th...
Article
Full-text available
Background & Aim Upon local delivery, MSCs aggregate into spheroids leading to alterations in phenotype. While MSCs immunomodulatory potential in 2D cultures has been extensively studied, the effect of aggregation on this potential is less understood. Using a series of in vitro potency assays, we sought to evaluate changes to human MSCs ability to...
Article
A pilot study of COVID-19 patients treated with mesenchymal stem cells demonstrates safety.
Article
Lipid droplets (LDs) are frequently increased when excessive lipid accumulation leads to cellular dysfunction. Distinct from mouse beta cells, LDs are prominent in human beta cells, however, the regulation of LD mobilization (lipolysis) in human beta cells remains unclear. We found that glucose increases lipolysis in non-diabetic human islets, but...
Article
Lipid droplets (LDs) are frequently increased when excessive lipid accumulation leads to cellular dysfunction. Distinct from mouse beta cells, LDs are prominent in human beta cells, however, the regulation of LD mobilization (lipolysis) in human beta cells remains unclear. We found that glucose increases lipolysis in non-diabetic human islets, but...
Article
Some cell therapies increase the risk of thromboembolism in trauma patients due to high tissue factor expression.
Article
Full-text available
Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into “spheroids,” which alters gene expression and phenotype. While adherent MSCs are highly efficient in their inhibition of T cells, whether or not this property is altered upon MSC aggregation has not been...
Article
Full-text available
Mesenchymal stromal/stem cell (MSC) therapies have been employed in more than 800 registered clinical studies across the globe and there are now >55,000 publications readily available on MSCs. Their profound immunomodulatory and regenerative properties have made MSCs one of the most promising and intensely pursued cellular therapies. Although meta-...
Article
Full-text available
Objective T-box 1 (TBX1) has been identified as a genetic marker of beige adipose tissue. TBX1 is a mesodermal development transcription factor essential for tissue patterning and cell fate determination. However, whether it plays a role in the process of adipose beiging or how it functions in adipose tissue has not been reported. Here, we examined...
Preprint
Full-text available
Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon gamma exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory pote...
Article
Full-text available
As MSC products move from early development to clinical translation, culture conditions shift from xeno- to xeno-free systems. However, the impact of isolation and culture-expansion methods on the long-term resiliency of MSCs within challenging transplant environments is not fully understood. Recent work in our lab has shown that palmitate, a satur...
Article
Full-text available
Background & Aims The lysosome is an acidic organelle that is important for maintaining cellular and metabolic homeostasis in hepatocytes. Lysosomal dysfunction and chronic inflammation coexist, and both contribute to obesity-associated hepatic insulin resistance. However, in the context of obesity, the interplay between inflammatory signals and he...
Article
Full-text available
Intravascular infusion is the most popular route for therapeutic multipotent mesenchymal stromal/stem cell (MSC) delivery in hundreds of clinical trials. Meta-analysis has demonstrated that bone marrow MSC infusion is safe. It is not clear if this also applies to diverse new cell products derived from other sources, such as adipose and perinatal ti...
Article
Mesenchymal stromal cells (MSCs) for basic research and clinical applications are manufactured and developed as unique cell products by many different manufacturers and laboratories, often under different conditions. The lack of standardization of MSC identity has limited consensus around which MSC properties are relevant for specific outcomes. In...
Article
The development of better methods to grow human tissue in conditions that more closely recapitulate normal physiology and anatomy (i.e. biomimetic technology) will greatly enhance drug and toxin testing as well as advance our understanding of biology. Two dimensional (2D) cell culture has been extremely valuable for research, but cells grown in 2D...
Article
Full-text available
s Rodent islets are widely used to study the pathophysiology of beta cells and islet function, however, structural and functional differences exist between human and rodent islets, highlighting the need for human islet studies. Human islets are highly variable, deteriorate during culture, and are difficult to genetically modify, making mechanistic...
Code
This macro measures the cross sectional area of spheroids/organoids and estimates the volume based on the major and minor axis of the cross section fit to an elipsoid. The nuclei were stained by incubating with 10 microg/ml Hoechst 33342 for 30 minutes at 37 ºC and 5% CO2. A Z-stack of images can then be analyzed by this imageJ macro “Measure Spher...
Article
https://www.nature.com/articles/d41586-018-05823-5?sf194594042=1
Article
Full-text available
Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D culture often does not reflect the complexity of fat tissue. Animal models are also problematic in that they are expensive, time consuming, and may not completely recap...
Article
The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2 diabetes (T2D) and T2D complications is promising; however, the investigation of MSC function in the setting of T2D has not been thoroughly explored. In our current study, we investigated the phenotype and function of MSCs in a simulated in vitro T2D environment. We show...
Chapter
Full-text available
Much of the in vitro study of organs relies on responses from monolayers composed of one or more cell types; however, in many cases, this simplistic modeling of the organ system does not replicate how cells behave in vivo in the context of their organ and organism. While many useful cell characteristics can be deduced from 2D cell cultures, a full...
Article
Objective: Techniques to validate successful delivery of cell products are expensive, time-consuming, and require transport of the animal to imaging facilities, preventing their widespread use as documentation tools. The goal of this study was to determine if a low-cost portable microscope could provide sufficient performance to be used to document...
Article
Full-text available
Abbreviations: CLI, critical limb ischemia; GvHD. graft versus host disease; I/R, ischemia reperfusion (I/R); OI, osteogenesis imperfecta.