Keith L March

Keith L March
Indiana University-Purdue University Indianapolis | IUPUI · Indiana Center for Vascular Biology and Medicine

MD, PhD

About

253
Publications
20,746
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
18,536
Citations
Citations since 2017
43 Research Items
5635 Citations
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
201720182019202020212022202302004006008001,000
Introduction
Skills and Expertise

Publications

Publications (253)
Article
As it begins to enter the clinic, regenerative medicine has the potential to revolutionize healthcare. Although there exists a growing need for individuals well-versed in the practice of regenerative medicine, few undergraduate institutions offer opportunities to learn about the topic. This article highlights the conception of two novel undergradua...
Article
Full-text available
Adipose tissue is widely recognized as an abundant and accessible human tissue that serves as a source of cells and extracellular matrix scaffolds for regenerative surgical applications. Increasingly, orthopedic surgeons are turning to adipose tissue as a resource in their treatment of osteoarthritis and related conditions. In the U.S., the regulat...
Article
Myocardial Infarction Diagnosis To address the limitations of current myocardial infarction (MI) detection technology, in article 2201330, Pinar Zorlutuna and co‐workers develop the human heart anoxia and reperfusion tissue (HEART) model combined with a near real‐time microRNAs (miRNAs) concentration sensor for analysis of miRNAs under MI condition...
Article
Current biomarkers for myocardial infarction (MI) diagnosis are typically late markers released upon cell death, incapable of distinguishing between ischemic and reperfusion injury and can be symptoms of other pathologies. Circulating microRNAs (miRNAs) have recently been proposed as alternative biomarkers for MI diagnosis; however, detecting the c...
Article
Full-text available
MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies show promise in decreasing mortality in acute respiratory distress syndrome (ARDS) and suggest benefits in treatment of COVID-19-related ARDS. We performed a meta-analysis of published trials assessing the efficacy and adverse events (AE) rates of MSC cell therapy in indi...
Article
Background Heart transplantation, a life-saving approach for patients with end-stage heart disease, is limited by shortage of donor organs. While prolonged storage provides more organs, it increases the extent of ischemia. Therefore, we seek to understand molecular mechanisms underlying pathophysiological changes of donor hearts during prolonged st...
Preprint
Full-text available
MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies have shown promise in decreasing mortality in ARDS and suggest benefits in treatment of COVID-19 related ARDS. We performed a meta-analysis of published trials assessing the effectiveness and adverse events (AE) of MSC cell therapy in individuals hospitalized for COVID-19...
Article
Exogenous cell-based therapy has emerged as a promising new strategy to facilitate repair of hearts damaged by acute or chronic injury. However, the field of cell-based therapy is handicapped by the lack of standardized definitions and terminology, making comparisons across studies challenging. Even the term “stem cell therapy” is misleading becaus...
Article
Full-text available
Aims CONCERT‐HF is an NHLBI‐sponsored, double‐blind, placebo‐controlled, Phase II trial designed to determine whether treatment with autologous bone marrow‐derived mesenchymal stromal cells (MSCs) and c‐kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by i...
Article
Background: Covid-19 has contributed to high mortality and morbidity among hospitalized patients. One of the main pathophysiological processes of the disease is an exuberant immune response leading to respiratory failure. MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies have shown promise in modulating responses in infl...
Article
Heart transplantation is a life-saving therapy for end-stage organ failure. Organ deterioration during transportation limits storage to 4 hours, limiting hearts available. Approaches ameliorating organ damage could increase the number of hearts acceptable for transplantation. Prior studies show that adipose-derived stem/stromal cell secretome (ASC-...
Article
Full-text available
Background: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment. Objectives: SENECA (Stem Cell Injection in Cancer Su...
Article
Full-text available
We have shown previously that adipose stromal cell (ASC)-derived conditioned media (CM) limited lung injury, endothelial barrier dysfunction, and apoptosis. Here, we used endothelial hyperpermeability and apoptosis assays to investigate how concentration processes affect endothelium-directed bioactivity of ASC-CM and to gain information on the natu...
Article
Although adipose tissue and cells show considerable promise for clinical translation in the emerging field of regenerative medicine, they present a challenge to the regulatory community both nationally and internationally. This has been exacerbated by recent high-profile cases involving adverse events attributed to adipose cell-based therapies. Thi...
Article
Background No specific therapy exists for acute pancreatitis (AP), and current treatment remains entirely supportive. Adipose stem cells (ASCs) have significant immunomodulatory and regenerative activities. We hypothesized that systemic administration of ASCs would mitigate inflammation in AP. Methods AP was induced in mice by 6 hourly intraperito...
Article
Full-text available
Influenza A virus (IAV) remains a major worldwide health threat, especially to high-risk populations, including the young and elderly. There is an unmet clinical need for therapy that will protect the lungs from damage caused by lower respiratory infection. Here, we analyzed the role of EMAPII, a stress- and virus-induced pro-inflammatory and pro-a...
Article
Full-text available
Background: Several inflammatory lung diseases display abundant presence of hyaluronic acid (HA) bound to heavy chains (HC) of serum protein inter-alpha-inhibitor (IαI) in the extracellular matrix. The HC-HA modification is critical to neutrophil sequestration in liver sinusoids and to survival during experimental lipopolysaccharide (LPS)-induced...
Article
We have shown that cigarette smoke (CS)-induced pulmonary emphysema-like manifestations are preceded by marked suppression of the number and function of bone marrow hematopoietic progenitor cells (HPC). To investigate if a limited availability of HPC may contribute to CS-induced lung injury, we used an FDA-approved antagonist of the interactions of...
Article
Full-text available
Rationale: Autologous bone marrow (BM) mesenchymal stem cells (MSCs) and c-kit+ cardiac progenitor cells (CPCs) are two promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans regarding the relative efficacy of MSCs and CPCs and whether their combination...
Article
Objectives SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). Background AIC is an incurable and often f...
Article
Cigarette smoking (CS) adversely affects the physiologic function of endothelial progenitor, hematopoietic stem and progenitor cells. However, the effect of CS on the ability of adipose stem/stromal cells (ASC) to promote vasculogenesis and rescue perfusion in the context of ischemia is unknown. To evaluate this, ASC from nonsmokers (nCS-ASC) and s...
Article
The interaction between human endothelial (EC) and adipose mesenchymal stem/stromal cells (ASC) leads to EC reorganization into stable vascular structures in vitro and functional vessels in vivo and ASC maturation from progenitor to smooth muscle/pericyte phenotype. We have previously shown that juxtacrine EC-ASC interactions induce in ASC to expre...
Article
Full-text available
Alpha-1 antitrypsin (A1AT), a circulating acute phase reactant anti-protease, is produced and secreted by cells of endodermal epithelial origin, primarily hepatocytes, and by immune cells. Deficiency of A1AT is associated with increased risk of excessive lung inflammation and injury, especially following chronic cigarette smoke exposure (CS). Exoge...
Article
Full-text available
Acute ischaemia causes a significant loss of blood vessels leading to deterioration of organ function. Multiple ischaemic conditions are associated with up-regulation of activin A, but its effect on endothelial cells (EC) in the context of hypoxia is understudied. This study evaluated the role of activin A in vasculogenesis in hypoxia. An in vitro...
Article
Background There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar...
Data
Figure S1 Gating strategies for the phenotypic analysis of infiltrating CD4+ T cells in the kidney. Lymphocytes were gated based on the forward scatter versus side scatter, which is further gated on CD4+/CD8+ T cells. Right column: These T cells were analyzed further based on the activation markers for IL‐17 (shown as histogram) or IL4 and IFNγ (sh...
Data
Figure S2 hASC fail to home to the kidney following ischemia reperfusion injury. Shown are representative confocal images of Celltracker‐CMTPX labeled ASCs in vitro just prior to injection (A) and in kidney (B and D) or lung (C and E) at 10 min. (B and C) or 48 hrs (D and E) following administration. No cells were detected in kidney at any time, wh...
Article
Full-text available
Damage to endothelial cells contributes to acute kidney injury (AKI) by causing impaired perfusion, while the permanent loss of the capillary network following AKI has been suggested to promote chronic kidney disease. Therefore, strategies to protect renal vasculature may impact both short-term recovery and long-term functional preservation post-AK...
Article
Full-text available
Background: Atherosclerotic peripheral artery disease affects 8% to 12% of Americans >65 years of age and is associated with a major decline in functional status, increased myocardial infarction and stroke rates, and increased risk of ischemic amputation. Current treatment strategies for claudication have limitations. PACE (Patients With Intermitt...
Article
Adipose tissue is a rich source of multipotent mesenchymal stem-like cells, located in the perivascular niche. Based on their surface markers, these have been assigned to two main categories: CD34+CD31-CD45-CD146- cells (adventitial stromal/stem cells, ASCs), and CD146+CD31-CD34-CD45- cells (pericytes, PCs). These populations display heterogeneity...
Article
Background: Early clinical trials of cell-based therapies in stroke have been very encouraging; however, technical hurdles may prevent widespread adoption. The salutary effects appear to be through release of “trophic” factors and immunomodulators which affect host repair and protection responses. We are developing a novel stroke therapy which is a...
Article
Background: The progressive decline in tissue mechanical strength that occurs with aging is hypothesized to be due to a loss of resident stem cell number and function. As such, there is concern regarding use of autologous adult stem cell therapy in older patients. To abrogate this, many patients elect to cryopreserve the adipose stromal-vascular f...
Article
Adipose stromal cells (ASCs) support endothelial cell (EC) vasculogenesis through paracrine and cell-contact communications. In addition, ASCs differentiate towards the smooth muscle cell (SMC) phenotype under different stimuli, which prompted their use as a source of mural cells in fabricating small calibre vessels. How ASCs' SMC-lineage commitmen...
Article
Full-text available
Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associ...
Article
Full-text available
Unlabelled: Adipose-derived stem cells (ASC) have received considerable attention in oncology because of the known direct link between obesity and cancer as well as the use of ASCs in reconstructive surgery after tumor ablation. Previous studies have documented how cancer cells commandeer ASCs to support their survival by altering extracellular ma...
Article
Full-text available
Adipose tissue is an attractive source of mesenchymal stem cells (MSC) as it is largely dispensable and readily accessible through minimally invasive procedures such as liposuction. Until recently MSC could only be isolated in a process involving ex-vivo culture and their in-vivo identity, location and frequency remained elusive. We have documented...
Article
Background: Intestinal ischemia can quickly escalate to bowel necrosis and perforation. Transplantation of stem cells presents a novel treatment modality for this problem. We hypothesized that: (1) Human adipose derived stromal cells (hASCs) would increase survival and mesenteric perfusion to a greater degree compared to differentiated cellular co...
Article
Full-text available
Acute Respiratory Distress Syndrome (ARDS) is a condition that contributes to morbidity and mortality of critically ill patients. We investigated whether factors secreted by adipose stromal cells (ASC) into conditioned media (ASC-CM) will effectively decrease lung injury in the model of lipopolysaccharide (LPS)-induced ARDS. To assess the effect of...
Article
Full-text available
Transplantation of mesenchymal stromal cells (MSC) has been shown to effectively prevent lung injury in several preclinical models of Acute Respiratory Distress Syndrome (ARDS). Since MSC therapy is tested in clinical trials for ARDS, there is an increased need to define the dynamics of cell trafficking and organ-specific accumulation. We examined...
Article
Full-text available
Adipose stromal cells (ASC) secrete various trophic factors that assist in the protection of neurons in a variety of neuronal death models. In this study, we tested the effects of human ASC conditional medium (ASC-CM) in human amyotrophic lateral sclerosis (ALS) transgenic mouse model expressing mutant superoxide dismutase (SOD1(G93A)). Treating sy...
Article
Full-text available
Transplantation of adipose-derived stem cells (ASC) is an emerging therapeutic option for addressing intractable diseases such as critical limb ischemia (CLI). Evidence suggests that therapeutic effects of ASC are primarily mediated through paracrine mechanisms rather than transdifferentiation. These secreted factors can be captured in conditioned...
Article
Adipose stem/stromal cells (ASC) after isolation produce numerous angiogenic growth factors. This justifies their use to promote angiogenesis per transplantation. In parallel, local co-implantation of ASC with endothelial cells (EC) leading to formation of functional vessels by the donor cells suggests the existence of a mechanism responsible for f...
Article
Stem cells have demonstrated promise in early clinical trials evaluating safety, feasibility, and effectiveness for treating stroke. It is becoming increasingly clear that the mechanism of action by which multipotent adult stem cells address the complex pathophysiology of stroke is not predominantly their ability to differentiate into cell types th...
Article
Objective: Abdominal aortic aneurysm (AAA) formation is characterized by activation of innate and adaptive immune responses that initiate aortic wall degradation. We hypothesize that human adipose stromal cells (ASC) favorably modulate these immune responses through paracrine mechanisms and attenuate AAA expansion in a murine elastase model. Method...
Article
Introduction: Abdominal aortic aneurysm (AAA) formation is characterized by activation of innate and adaptive immune responses that initiate aortic wall degradation. We hypothesize that human adipose stromal cells (ASC) favorably modulate these immune responses through paracrine mechanisms and attenuate AAA expansion in a murine elastase model. Met...
Article
Full-text available
Objective: Bone marrow-derived hematopoietic stem and progenitor cells (HSC/HPC) are critical to homeostasis and tissue repair. The aims of this study were to delineate the myelotoxicity of cigarette smoking (CS) in a murine model, to explore human adipose-derived stem cells (hASC) as a novel approach to mitigate this toxicity, and to identify key...
Article
Full-text available
Adipose tissue stroma contains a population of mesenchymal stem cells (MSC) promote new blood vessel formation and stabilization. These adipose-derived stem cells (ASC) promote de novo formation of vascular structures in vitro. We investigated the angiogenic factors secreted by ASC and discovered that glial-derived neurotrophic factor (GDNF) is a k...
Article
Autologous adipose stem cell transplantation is increasingly being used for soft tissue reconstruction, particularly after mastectomy. However, a recent study demonstrated recurrence of invasive ductal carcinoma in the breast within four months of autologous fat grafting. Previous studies have documented how cancer cells commandeer adipose stem cel...
Article
Rationale: Adipose stromal cells (ASC) are therapeutically potent progenitor cells that possess properties of pericytes. In vivo, ASC in combination with endothelial cells (EC) establish functional multilayer vessels, in which ASC form the outer vessel layer and differentiate into mural cells. Objective: To identify factors responsible for ASC d...
Article
Adipose-derived stromal/stem cells (ASCs) ameliorate hyperglycemia in rodent models of islet transplantation and autoimmune diabetes, yet the precise human ASC (hASC)-derived factors responsible for these effects remain largely unexplored. Here, we show that systemic administration of hASCs improved glucose tolerance, preserved β cell mass, and inc...
Article
Objectives The potential for beneficial effects of adipose-derived stem cells (ASCs) on myocardial perfusion and left ventricular dysfunction in myocardial ischemia (MI) has not been tested following intravenous delivery.Methods Surviving pigs following induction of MI were randomly assigned to 1 of 3 different groups: the placebo group (n = 7), th...
Article
Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Strept...
Article
Objectives: To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. Background: Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mo...
Article
Full-text available
Most solid tumors, including pancreatic ductal adenocarcinoma (PDAC), exhibit structural and numerical chromosome instability (CIN). While often implicated as a driver of tumor progression and drug resistance, CIN also reduces cell fitness and poses a vulnerability which can be exploited therapeutically. The spindle assembly checkpoint (SAC) ensure...
Article
Full-text available
Background aims: Adipose tissue is a rich and very convenient source of cells for regenerative medicine therapeutic approaches. However, a characterization of the population of adipose-derived stromal and stem cells (ASCs) with the greatest therapeutic potential remains unclear. Under the authority of International Federation of Adipose Therapeuti...
Article
Recent clinical trials indicate that human adipose-derived stromal cells (hASCs) have beneficial effects on antiaging and wound healing. This study examined the morphologic changes in photodamaged human organotypic skin culture after treatment of autologous hASCs. Abdominal skin flaps were obtained from 8 white females who underwent abdominoplastie...
Article
Introduction: Autologous bone marrow mesenchymal stromal cells (ABMSCs) have been the focus for the treatment of myocardial and limb ischemia. The utility of ABMSCs is limited because, in addition to requiring an invasive procedure to harvest, the number and the regenerative capacity of ABMSCs decrease with age and comorbid conditions. A redirected...