Breaking News
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
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