CMV Infections Increase Complications and Costs After Stem Cell Transplantation

MedicalResearch.com Interview with:

Dr. Jonathan Schelfhout, PhD Director, Outcomes Research Merck & Co. Inc. North Wales, PA

Dr. Schelfhout

Dr. Jonathan Schelfhout, PhD
Director, Outcomes Research
Merck & Co. Inc.
North Wales, PA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The cost of hematopoietic stem cell transplantation has received increased attention after it was identified as a top 10 contributor to increasing healthcare costs in an AHRQ 2016 report. Many recent studies have explored the cost of HSCT but additional research is needed on the costly complications that can follow the transplant procedure. This research is particularly relevant for inpatient decision makers, as most transplant centers receive one bundled payment for the transplant and the treatment of any complications over the first 100 days.

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American CryoStem – CRYO – Allows Individuals to Collect, Freeze and Store Their Stem Cells

MedicalResearch.com Interview with:

John Arnone, Chairman and CEO American CryoStem Corporation

John Arnone

John Arnone
Chairman and CEO

American CryoStem Corporation

MedicalResearch.com: What is the background for this your company American CryoStem?

Response: American CryoStem Corporation (CRYO) was founded in 2008, to allow individuals, researchers and physicians to collect-process-store stem cells derived from adipose tissue (fat) to prepare for their current or future use. Over the years the Company has become a biotechnology pioneer, standardizing adipose tissue derived technologies (Adult Stem Cells) for the fields of Regenerative and Personalized Medicine.

The Company operates a state-of-art, FDA-registered, clinical laboratory in New Jersey and licensed laboratories in Hong Kong, China and Tokyo, Japan, which operate on our proprietary platform, dedicated to the collection, processing, bio-banking, culturing and differentiation of adipose tissue (fat) and adipose derived stem cells (ADSCs)

CRYO maintains a strategic portfolio of intellectual property, 18 patents that surround the Companies proprietary technology which supports a growing pipeline of stem cell applications and biologic products. We are leveraging our proprietary platform and our developed product portfolio to create a domestic and global footprint of licensed laboratory affiliates, physicians networks and research organizations who purchase tissue collection, processing and storage services and consumables from the Company.

CRYO’s laboratory stem cell bank/line products are characterized adult human Mesenchymal Stem Cell (MSC’s) derived from adipose tissue that work in conjunction with our 13 patented (non-animal) medium lines.

The Company’s R&D efforts are focused on university and private collaborations to discover, develop and commercialize ADSC therapies by utilizing our standardized collection-processing-storage methodology and laboratory products combined with synergistic technologies to create jointly developed regenerative medicine applications and intellectual property.

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H. pylori May Increase Risk of Stomach Cancer By Turning On Subset of Stem Cells

MedicalResearch.com Interview with:
Michael Sigal PhD

Clinical scientist of the Charité — Universitätsmedizin Berlin
Investigator at the Max Planck Institute for Infection Biology 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have previously found that H. pylori can colonize gastric glands and that in colonized glands the epithelial turnover was increased. We wanted to characterize the mechanisms that control the gland turnover in the stomach.

We found that Axin2, a classic Wnt target gene, marks two different subpopulations of cells with stem cell properties, one of which is Lgr5-positive and the other one Lgr5-negative. Both populations are affected by Rspondin 3, that is produced in myofibroblasts right beneath the stem cell compartment. Rspondin is crucial for stem cell signaling and knockout of Rspondin 3 in myofibroblasts results in loss of Lgr5 and Axin2 expression. Once we increased the bioavailability of Rspondin, that now could also interact with cells outside of the stem cell compartment, we noticed that the number of Axin2 positive stem cells dramatically increased. Of interest, only Lgr5-negative cells expanded in number and proliferate more, while the Lgr5-positive cells remained silenced.

Infection with Helicobacter pylori leads to an expansion of Axin2-positive cells which is driven by increased expression of Rspondin3. Expansion of the long lived stem cell pool could be an explanation for how H. pylori infection increases the risk for gastric cancer.

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Skin-Grafted Stem Cells May Treat Obesity and Diabetes

MedicalResearch.com Interview with:

Dr. Xiaoyang Wu PhD Ben May Department for Cancer Research The University of Chicago, Chicago, IL

Dr. Xiaoyang Wu

Dr. Xiaoyang Wu PhD
Ben May Department for Cancer Research
The University of Chicago, Chicago, IL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We have been working on skin somatic stem cells for many years. As one of the most studies adult stem cell systems, skin stem cells have several unique advantages as the novel vehicle for somatic gene therapy (summarized also in the paper). The system is well established. Human skin transplantation using CEA device developed from skin stem cells have been clinically used for decades for burn wound treatment, and been proven to be safe the effective.

In this study, we developed a skin 3D organoid culture model to induce stratification and maturation of mouse epidermal stem cells in vitro, which allows us to efficiently transfer engineered mouse skin to isogenic host animals. In the proof of concept study, we showed that we can achieve systematic release of GLP1 at therapeutic concentration by engineered skin grafts.

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Unregulated Direct-to-Consumer Treatment Centers Provide Stem Cells for Patients With Heart Failure

MedicalResearch.com Interview with:

Dr. Paul J. Hauptman, MD Professor of Internal Medicine Division of Cardiology Assistant Dean, Clinical and Translational  Research Saint Louis University School of Medicine St. Louis MO 63110-0250

Dr. Hauptman

Dr. Paul J. Hauptman, MD
Professor of Internal Medicine
Division of Cardiology
Assistant Dean, Clinical and Translational  Research
Saint Louis University School of Medicine
St. Louis MO 63110-0250 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A publication in 2016 by Leigh Turner from the University of Minnesota in 2016 shed light on the proliferation of stem cell centers or “businesses” that offer non FDA approved treatments, described as “stem cell therapy” for a variety of conditions. We opted to evaluate sites that claimed to treat heart failure. We collected data on type of infusion, need for a medical evaluation, board certification status of the center physician, cost and other factors. Self reported patient volumes were very variable. Most centers/businesses claimed to use autologous stem cells; a number offered ancillary treatment (i.e. vitamin infusions and hyperbaric oxygen); only one appeared to have a board-certified cardiologist involved. The costs were high for single infusions (mean price of $7694, SD 2737 for autologous cells; slightly less for allogeneic cells). Efficacy claims made during telephone calls with the centers were highly positive.

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Preclinical Study Finds Cancer Stem Cell Inhibitor Sensitizes Colon Cancer Cells To Immunotherapy

MedicalResearch.com Interview with:
Dr. Yuan Gao

Assistant Investigator at Boston Biomedical

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Colorectal cancer (CRC) is the third most commonly diagnosed malignant disease and third most frequent cause of cancer-related death in the United States. Standard treatment for unresectable metastatic CRC currently includes first and second line 5-fluorouracil (5-FU)-based chemotherapy regimens. However, CRC patients often develop chemoresistance. Recently, immunotherapy has emerged as a revolutionary new treatment for CRC. However, with the exception of a small percentage of CRC patients that display microsatellite instability (MSI), the vast majority of colorectal cancer patients have been found to be resistant to immune checkpoint therapies.

Cancer stem cells (CSCs), a highly malignant tumor cell subpopulation capable of self-renewal, are considered to be fundamentally responsible for malignant growth and tumor recurrence. Emerging evidence indicates that CSCs and cancer stemness pathways, such as STAT3, beta-Catenin, CD44 and Nanog, are involved in the immune evasion of cancers. BBI-608 (napabucasin) is an orally-administered first-in-class cancer stemness inhibitor that works by targeting STAT3. In this study, we investigated the effect of cancer stemness inhibition on sensitizing colorectal cancer to immune checkpoint inhibitors in preclinical models.

In the syngeneic microsatellite stable (MSS) tumor model, CT26, an anti-PD-1 antibody delivered as a monotherapy, produced low level and temporary antitumor activity with rapid development of complete resistance to anti-PD-1 treatment. The anti-PD-1 antibody-treated CT26 tumors exhibited increased p-STAT3 activation and overexpression of a variety of stemness factors, as well as enrichment of sphere-forming stemness-high cancer cells. Napabucasin was able to reduce basal as well as anti-PD1-induced STAT3 activation and other CSC features within CT26 tumors. The combination of a stemness inhibitor – napabucasin – with the anti-PD-1 antibody led to tumor complete response (CR) in all treated CT26 tumors, with 40 percent of the mice remaining tumor-free for 30 days following treatment termination. This combination also had a synergistic effect on the influx of tumor infiltrating CD8+ T cells, which likely contributed to the rapid tumor regression. Finally, mice CR-induced by napabucasin and the anti-PD-1 antibody were able to reject CT26 tumors upon re-challenge, but not the unrelated breast cancer 4T1 tumors.

MedicalResearch.com: What should readers take away from your report?

Response: Our data suggest cancer stemness pathways contribute to immunotherapy resistance in MSS CRC, a subtype representing the vast majority of colorectal cancer cases. Furthermore, inhibition of cancer stemness by BBI-608 sensitizes colorectal cancer to immune checkpoint inhibition, producing striking regression in a large proportion of the tumors treated.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study provides compelling preclinical evidence to support the investigation of the combination of napabucasin with immune checkpoint inhibitors in CRC. While this study specifically investigated the combination with anti-PD-1, the combination with other immunotherapies could be studied as well.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation: AACR 2017 Abstract

Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Three Distinct Cardiac Stem Cell Populations Isolated from a Single Human Heart Biopsy

MedicalResearch.com Interview with:

Megan M. Monsanto, B.S. Joint Doctoral Student Department of Cell and Molecular Biology San Diego State University & University of California San Diego

Megan Monsanto

Megan M. Monsanto, B.S.
Joint Doctoral Student
Department of Cell and Molecular Biology
San Diego State University &
University of California San Diego

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In the field of cardiovascular research there is ongoing debate regarding the optimal cell population(s) to use for the treatment of patients with heart failure. A major reason being, the lack of understanding of the actions and synergism between distinct myocardial-derived stem cell populations. This prompted our group to establish a protocol to isolate multiple stem cell populations from a single human myocardial tissue sample that will allow for the discovery of new insights at the cellular level, with the ultimate goal being to achieve true myocardial regeneration upon injection back into the patient.

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Human Stem Cells Can Be Used For 3-D Printing of Tissue Stuctures

MedicalResearch.com Interview with:

Sang Jin Lee, Ph.D. Associate Professor of Wake Forest Institute for Regenerative Medicine Wake Forest School of Medicine Wake Forest University

Dr. Sang Jin Lee

Sang Jin Lee, Ph.D.
Associate Professor of Wake Forest Institute for Regenerative Medicine
Wake Forest School of Medicine
Wake Forest University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: I received my Ph.D. in Chemical Engineering at Hanyang University, Seoul, South Korea in 2003 and took a postdoctoral fellowship in the Laboratories for Tissue Engineering and Cellular Therapeutics at Harvard Medical School and Children’s Hospital Boston and the Wake Forest Institute for Regenerative Medicine where I am currently a faculty member. My research works have focused on development of smart biomaterial systems that support the regenerative medicine strategies and approaches. These biomaterial systems combined with drug/protein delivery system, nano/micro-scaled topographical feature, or hybrid materials that could actively participate in functional tissue regeneration. Recently my research works utilize 3D bioprinting strategy to manufacture complex, multi-cellular living tissue constructs that mimic the structure of native tissues. This can be accomplished by optimizing the formulation of biomaterials to serve as the scaffolding for 3D bioprinting, and by providing the biological environment needed for the successful delivery of cells and biomaterials to discrete locations within the 3D structure.

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RepliCel Developing Autologous Cell Therapies For Skin, Hair and Tendon Regeneration

MedicalResearch.com with:

Lee Buckler, CEO
RepliCel Life Sciences

MedicalResearch.com: What is the background for this your company, RepliCel.com?

Response: RepliCel Life Sciences is a Canadian regenerative medicine company based in Vancouver, British Columbia that was founded in 2006. The company focuses on the development of cell therapies using a patient’s own cells (autologous cell therapy). It is developing treatments targeted at healing chronic tendon injuries that have failed to heal properly, hair restoration, and the treatment of damaged and aged skin.

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Process Refines Conversion of Skin Fibroblasts into Cardiac Blood Vessels

MedicalResearch.com Interview with:

Jalees Rehman, MD Director of Research, Division of Cardiology Associate Professor of Medicine and Pharmacology University of Illinois at Chicago College of Medicine Chicago, IL 60612

Dr. Rehman

Jalees Rehman, MD
Director of Research, Division of Cardiology
Associate Professor of Medicine and Pharmacology
University of Illinois at Chicago
College of Medicine
Chicago, IL 60612

MedicalResearch.com: What is the background for this study?

Response: Converting skin fibroblasts into regenerative blood vessel endothelial cells could be a valuable approach to repair diseased blood vessels in patients with cardiovascular disease and also to build new blood vessels in order to supply engineered tissues and organs.

Using skin fibroblasts is very well suited for personalized therapies because they can be obtained from a skin biopsy in an outpatient setting. The biopsied skin sample is used to extract the skin fibroblasts, which are then expanded in cell culture dishes before they are converted to endothelial cells. This allows for the generation of tens or hundreds of millions of cells that will likely be needed for blood vessel repair and regeneration. By converting skin fibroblasts of a patient, we can generate personalized endothelial cells with the same genetic signature as the patient so that they are less likely to be rejected if implanted back into the same patient after the conversion.

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