Breaking News
April 18, 2019 - Hickenlooper Expanded Medicaid, Created State-Run Marketplace To Insure Nearly All Coloradans
April 18, 2019 - Cancer cells grown in tumor-mimicking environment can help predict the effect of experimental drugs
April 18, 2019 - Albireo Announces FDA Clearance of IND to Commence Phase 2 Trial of Elobixibat for the Treatment of NAFLD/NASH
April 18, 2019 - Adhesive gel bonds to eye surface, could repair injuries without surgery
April 18, 2019 - The future of genomics: A podcast featuring Stanford geneticists
April 18, 2019 - As Syphilis Invades Rural America, A Fraying Health Safety Net Is Failing To Stop It
April 18, 2019 - APOE gene impacts sleep depending on gender and severity of Alzheimer’s
April 18, 2019 - PCORI’s newly approved awards focus on cancer pain and opioid use disorders
April 18, 2019 - New tool provides a standard way to measure effects of caring for survivors of TBI
April 18, 2019 - Smartphone use risks eye examination misdiagnosis
April 18, 2019 - How drug-resistant bugs grow in CF patients’ lungs
April 18, 2019 - Gordana Vunjak-Novakovic Elected to American Academy of Arts & Sciences
April 18, 2019 - Podcast: KHN’s ‘What The Health?’ You Have Questions, We Have Answers
April 18, 2019 - Diabetic drug shows potential to be repurposed as heart disease treatment for non-diabetic patients
April 18, 2019 - New estimation method assesses natural variations in sex ratio at birth
April 18, 2019 - UTA scientist receives $1.17 million grant for cancer research
April 18, 2019 - Coagulation factor VIIa prevents bleeds in hemophilia animal models
April 18, 2019 - Researchers identify risk factors for severe infection after knee replacement
April 18, 2019 - Mass drug administration can offer community-level protection against malaria
April 18, 2019 - FDA’s added sugar label could have substantial health and cost-saving benefits
April 18, 2019 - Researchers identify cause of inherited metabolic disorder
April 18, 2019 - Single strip of white paint not sufficient to protect people who ride bikes
April 18, 2019 - Partner status influences link between sexual problems and self-efficacy in breast cancer survivors
April 18, 2019 - Colorectal Neoplasia Risk Up for Hodgkin Lymphoma Survivors
April 18, 2019 - Rigid spine muscular dystrophy – Genetics Home Reference
April 18, 2019 - Simple bile acid blood test could tell risk of stillbirth
April 18, 2019 - Center for Experimental Therapeutics aims to enable all steps of drug development | News Center
April 18, 2019 - Falling for telephone scams could be an early sign of dementia
April 18, 2019 - Researchers annotate key neuronal proteins in lamprey genome
April 18, 2019 - Study uncovers new biomarker for personalized cancer treatments
April 18, 2019 - Scientists enter research collaboration to find a cure for cancer
April 18, 2019 - Study to compare benefits of tai chi and mindfulness meditation on MS symptoms
April 18, 2019 - Gestational diabetes during pregnancy may increase risk of type 1 diabetes in children
April 18, 2019 - Is a New Remedy for Body Odor on the Horizon?
April 18, 2019 - Orthostatic hypotension – Genetics Home Reference
April 18, 2019 - Healing the heartbreak of stillbirth and newborn death
April 18, 2019 - Conference to highlight advances in human immune monitoring, bioinformatics | News Center
April 18, 2019 - Bacteria use viruses for self-recognition, study reveals
April 18, 2019 - New adhesive patch could help reduce post-heart attack muscle damage
April 18, 2019 - Researchers analyze the effects of dark play in a serious video game
April 18, 2019 - Scientists revive pig brain cells four hours after death
April 18, 2019 - Filial cannibalism and offspring abandonment may be forms of parental care
April 18, 2019 - Two proteins act in concert to maintain a healthy heart in mice, shows study
April 18, 2019 - Scientists create a functioning 3D printed heart
April 18, 2019 - Non-invasive vagus nerve stimulation improves disease symptoms in patients with rheumatoid arthritis
April 18, 2019 - Majority of men struggle to understand diagnosis and treatment of prostate cancer
April 18, 2019 - Researchers create new small molecules that may combat equine encephalitis viruses
April 18, 2019 - Animal-assisted therapy improves social behavior in patients with brain injuries
April 18, 2019 - Some viruses help protect harmful bacteria in CF patients | News Center
April 18, 2019 - Outpatient healthcare providers inappropriately prescribe antibiotics to 40% of patients
April 18, 2019 - Men who have a resting heart rate of 75 bpm are twice as likely to die early
April 18, 2019 - Novel serum biomarkers to detect NAFLD-related fibrosis
April 18, 2019 - New study delves deeper into individual genomic differences than ever before
April 18, 2019 - Gilead and Galapagos Announce Filgotinib Meets Primary Endpoint in the Phase 3 FINCH 3 Study in Methotrexate-Naïve Rheumatoid Arthritis Patients
April 18, 2019 - Emotional mirror neurons found in rats
April 18, 2019 - Sylvia Plevritis appointed chair of biomedical data science | News Center
April 18, 2019 - Cervical cancer subtype increasing in several subpopulations of women
April 18, 2019 - Yeast strain provides manufacturing boost to low-calorie sweetener derived from lactose
April 18, 2019 - One in five children and youth suffer from a mental disorder
April 18, 2019 - Improper inhaler use common in children with asthma
April 18, 2019 - C-Path and CDISC release global Therapeutic Area Standard for HIV research
April 18, 2019 - Integrating AI to analyze imaging data allows early recognition of heart disease
April 18, 2019 - Low-cost, high-speed algorithm may allow animal-free chemical toxicity testing
April 18, 2019 - HPV-negative cervical cancers are more aggressive with worse prognosis
April 18, 2019 - AI detects prostate cancer with same level of accuracy as experienced radiologists
April 18, 2019 - Study resolves sex differences in psychiatric illness risk
April 18, 2019 - Novartis Announces FDA Filing Acceptance and Priority Review of Brolucizumab (RTH258) for Patients with Wet AMD
April 18, 2019 - Cocktail of common antibiotics can fight resistant E. coli
April 18, 2019 - Persis Drell to give keynote address at medical school diploma ceremony | News Center
April 18, 2019 - EpicTogether: Remembering Our Why
April 18, 2019 - Study identifies novel loci contributing to asthma susceptibility in adults
April 18, 2019 - Gut bacteria and pregnancy
April 18, 2019 - New study finds that screening could help prevent rare types of cervical cancer
April 17, 2019 - Spatial orgnization of the genome can be altered using small molecules
April 17, 2019 - AEDs Tied to Higher Pneumonia Risk in Alzheimer Patients
April 17, 2019 - Telemedicine tied to more antibiotics for kids, study finds
April 17, 2019 - Two medical students awarded 2019 Soros Fellowships for New Americans | News Center
April 17, 2019 - Sociologist Constance A. Nathanson Awarded Guggenheim Fellowship
April 17, 2019 - Empathy and hormones could account for aggressive behavior in children, shows study
April 17, 2019 - Researchers develop oral appliance to help sufferers of sleep apnea
Transplanting mismatched organs may be possible — and safe — in the future, new findings suggest

Transplanting mismatched organs may be possible — and safe — in the future, new findings suggest

image_pdfDownload PDFimage_print

For those hoping for a new heart, liver, bone marrow or other organ, the wait for a compatible organ has always been part of the excruciating drama of transplantation. If an organ isn’t tissue-matched, that is to say, looks immunologically enough like the patient’s own tissue, the patient’s body will likely reject it. Even when the organ is a close match, there are enough differences that the organ recipient will likely have to take anti-rejection drugs potentially for life. These drugs have toxic side effects and leave patients vulnerable to infection.

All of this may change in the future, thanks to a set of collaborative discoveries by Stanford stem cell specialist and pediatrician Agnieszka Czechowicz, MD, PhD, and her colleagues at Stanford, Harvard, Boston Children’s Hospital, and the National Institute of Allergy and Infectious Diseases. Czechowicz began the work as a graduate student in the laboratory of Irving Weissman, MD, who directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine. She continued her research during her residency and fellowship at the Dana Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center before returning to Stanford as a faculty member.

In a pair of papers published in the journal Nature Communications, the researchers show that they can attach a drug to an antibody called anti-CD117 that can selectively search out and eliminate blood-producing stem cells in mice. This is important because other studies in animals and humans have shown that replacing blood-producing stem cells with a donor’s blood-producing stem cells can facilitate the immune acceptance of tissues from that same donor. Unfortunately, current methods of eliminating blood-producing stem cells rely on toxic levels of chemotherapy and/or radiation that not only have both acutely damaging and long-lasting side effects, but also leave the recipient vulnerable to infection while the transplanted cells engraft.

In the first study, Czechowicz and her colleagues show that the drug-antibody compound can effectively and specifically eliminate blood-producing stem cells in a mouse without major side effects. Once eliminated, the researchers could replace the original blood-producing stem cells with others from an immunologically identical donor animal.

As described in a press release about the research from Boston Children’s Hospital:

The first study showed that a single dose of the antibody-drug combination eliminated more than 99 percent of blood-forming stem cells in mice. This allowed high levels of transplanted stem cells to take up residence in the host animals and effectively replace their blood and immune systems. Importantly, the antibody-drug conjugate specifically targeted the hosts’ stem cells without harming other kinds of blood cells and without causing clinically significant side effects. The animals’ immune cell function was preserved and responded effectively to pathogens.

That’s exciting news for clinicians who currently rely on blood-forming stem cell transplants to cure their patients of a variety of blood and immune disorders including cancer. It’s also exciting news for those developing blood-forming stem cell gene therapies, as this treatment could also enable safe engraftment of gene-modified cells.

But there’s more. The researchers  went on to demonstrate in the second paper that this drug-antibody conjugate in combination with a short-course of immune suppression can also be used to replace a mouse’s blood-producing stem cells with donor stem cells that do not match the recipient.

“The result is a chimera — a mix of original and transplanted blood stem cells — in the recipient,” Czechowicz said. Mice with these mixed blood and immune cells did not develop any complications and were able to accept a skin transplant from the stem-cell donor even many months later, the researchers found.

As Czechowicz explained in the Boston Children’s release:

Transplants of blood-forming stem cells not only create new blood and immune systems, they also lead to tolerance of other donor tissues and organs without the need for chronic immune suppression. But this approach isn’t used often, since it has, until now, required toxic radiation or chemotherapy pretreatment. Our modified approach could be transformative for the transplant field, and could potentially enable both stem cell transplantation and subsequent solid organ transplantation from any type of donor.

Czechowicz and her colleagues caution that this work has so far only been done in mice and has yet to be proven in human clinical trials. However, the research shows that it may be possible someday to safely and easily restore blood and immune functioning with no chemotherapy or radiation, and moreover then give patients an organ from a mismatched donor with minimal immunosuppression.

Photo by Louis Reed

Tagged with:

About author

Related Articles