Recently a new parer was published by the R&D Department of Biohellenika, usind the cord blood to develop autologous immunotherapies
Аn optimized, simplified and clinically approved culture system to produce, in large scale, dendritic cells capable of priming specific T cells
Eleni Gounari a,b,*, Nikolaos Tsagias a, Angelos Daniilidis c, Kokkona Kouzi a,d, George Koliakos a,b
Differentiation, 125 (2022): 54–61
a Biohellenika Biotechnology Company, Thessaloniki, Greece
b Department of Biochemistry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
c 2nd Department of Obstetrics and Gynecology, Hippokratio General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
d Department of Histology Embryology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
Keywords: Dendritic cells Hematopoietic stem cells Specific T-cells Colorectal cancer (CRC) Cancer immunotherapy
A B S T R A C T
Cancer immunotherapy using dendritic cells (DCs) able to induce specific immune responses to naïve T lymphocytes raises great research interest. However, the extremely complex and expensive methods used to produce DCs, combined with the limited number of autologous DCs in the circulation make any application almost impossible. Aim of the study is the development of an optimized and simplified system to easily produce in large scale cord blood-derived DCs, loaded with common tumor antigens, capable of promoting controlled Th1 immunoresponses following clinically approved maturation with vaccines. CD34+cells cultured in the presence of a cytokine cocktail in miniPERM® bioreactors and the generated DCs were matured using anti-flu vaccines. Autologous T cells plated with DCs pulsed with overlapping peptides CEA and WT1 for multiple stimulations. 200 billion of myeloid DCs were produced and matured in just 8 h in bioreactors, presenting an increased expression of the co-stimulatory molecules and also high levels of Th1 related cytokines. Upon just the 2nd stimulation, the T cells exhibited specificity following stimulation with the CEA/WT1 peptides and strong cytotoxic capacity in co-culture with a colorectal cancer (CRC)-cell line. The high produced doses of DCs, easily maturated with clinically approved agents, and capable of priming specific T cells, could potentially strengthen the further progress in DCs-mediated cancer immunotherapy field.
Stroke patient recovers after cord blood infusion from StemCyte
March 2022 Jonas Wang, PhD, & Bill Williams StemCyte is excited to announce the remarkable recovery of a patient who had been paralyzed on one side of his body as the result of a stroke. This patient received an infusion of a matching cord blood unit from the StemCyte public bank. Within a year, he had regained full motor function and images of his brain show that the swelling caused by the stroke had resolved. This case report was published in the peer-reviewed scientific journal CELL TRANSPLANTATION on 23 December 2021.
Acute stroke is the 2nd leading cause of death and 3rd leading cause of disability worldwide1. More than 15 million people suffer from a stroke annually. Approximately 30% - 35% of these patients die and nearly 75% of survivors sustain permanent disability. In ischemic stroke, a blood vessel in the brain is blocked. The best current treatment for ischemic stroke is to infuse thrombolytic agents to break down blood clots and increase blood flow to the brain. However, this intervention is strongly time-dependent: for every minute that treatment is delayed, 2 million nerve cells die in the patient’s brain2. In the United States, the optimal time window for stroke intervention has been dubbed the “Golden Hour” after onset of stroke. StemCyte registered a clinical trial NCT02433509 in cooperation with doctors at Taiwan’s Tzu Chi University Hospital that was designed to test the ability of cord blood infusions to help stroke patients. Although the trial was first registered in 2015, it has been difficult to enroll patients because of the requirement that they must find ischemic stroke victims that had missed the window for administration of anti-clotting drugs. The goal of the researchers is to measure the impact of the cord blood infusion alone, with no other stroke intervention in the patient’s system. In June of 2019, a 46-year-old male patient came to the hospital suffering from a stroke that had begun two hours earlier. This patient had a history of chronic high blood pressure and had been on dialysis for end stage kidney disease since 2011. The doctors realized that he was a candidate for the cord blood study and immediately obtained a baseline MRI image of his brain. Cord blood stem cells have several advantages over products that must be manufactured from the blood of the patient or from adult donors. There are the obvious practical advantages that cord blood products are already in storage, without having to find a donor, collect cells from the donor, and screen for diseases. Plus, cord blood products are much less likely to trigger a graft versus host reaction than blood cells from adult donors. Moreover, the authors of the StemCyte study present evidence that cryopreserved cord blood is significantly richer than adult blood in anti-inflammatory proteins that enable cells to communicate and significantly richer in cell growth factors1. StemCyte found a cord blood unit that matched the 46-year-old stroke patient at 6 out of 6 HLA types. The cord blood came from a baby that was born in Taiwan in July 2002, 17 years earlier! The cord blood had been processed with a plasma depletion method and had a total mononuclear cell count of 263 million. By the time the unit had been tested, transferred, thawed, and prepared for infusion, it was given to the patient on the 8th day after his stroke. In addition, the patient received four 100mL infusions of mannitol, starting a half hour after the cord blood and every 4 hours thereafter. Mannitol is a diuretic that is frequently given to patients suffering from traumatic brain injury, to lower their intracranial pressure. The images show magnetic resonance images (MRIs) of the stroke patient’s brain that were taken 2 hours after the stroke, 1 day after the umbilical cord blood (UCB) transfusion, 3 months after UCB transfusion, and 6 months after UCB transfusion. These MRI’s were taken with Diffusion-Weighted Imaging (DWI), which is a technique that highlights brain swelling and can accurately detect ischemic stroke within minutes of onset5. The images clearly show that the edema (swelling from excess fluid) in the right lobe of the patient’s brain disappeared within 6 months after the cord blood infusion. The true test of how well a therapy treats stroke is when a patient regains skills that had been impaired. In this case the patient was experiencing paralysis on the left side of his body (hemiplegia) as a result of the infarction on the right side of his brain. The patient began to regain mobility after the cord blood infusion, and by the third month he could walk with limited assistance. The patient was followed for one year following cord blood therapy. During this time his score on the NIH Stroke Scale (NIHSS) decreased from 9 to 1, the Berg Balance Scale score increased from 0 to 48; and the Barthel index which scores activities of daily living increased from 0 to 90 over the one year follow up. At the end of the observation period, the patient had fully recovered his motor functions and could live independently. Whereas most stroke patients are left with permanent disabilities, especially if they are not treated within the Golden Hour after stroke, this patient fully recovered after a simple cord blood infusion on the 8th day after his stroke. This could open a new landscape of hope for stroke patients around the world. This case report also demonstrates the potential value of cord blood donations sitting in public banks, even donations from decades ago. Whereas cord blood donations have long been promoted as a life-saving therapy for patients with blood cancers, they might have even broader application as a therapy for stroke patients.
StemCyte offers both public and private cord blood banking to parents in the United States, Taiwan, and India. To learn more about cord blood banking, visit Parent's Guide to Cord Blood Foundation at https://parentsguidecordblood.org/en/news/stroke-patient-recovers-after-cord-blood-infusion-stemcyte
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Stem cell transplantation may treat aggressive MS long term
WEST PALM BEACH, Fla. — Autologous hematopoietic stem cell transplantation had long-term effectiveness for treating aggressive MS, according to results of a retrospective observational study presented at the ACTRIMS Forum.
“The objective was to determine if the bone marrow transplant was effective and safe at long term,” Francis Brunet, of the MS clinic at Ottawa General Hospital in Canada, said during a presentation.
Specifically, Brunet and colleagues sought to examine whether autologous hematopoietic stem cell transplantation (aHSCT) led to durable disease remission and safety by analyzing short- and long-term outcomes from the Ottawa cohort. They retrospectively studied outcomes of 72 patients with aggressive MS who received aHSCT for MS at a single center between October 2001 and February 2021 and who were monitored for at least 6 months. Busulfan plus cyclophosphamide followed by anti-thymocyte globulin post-transplant of a CD34+ selected graft composed the conditioning regimen used for aHSCT.
The number of new clinical relapses following the transplant served as the primary outcome and new MRI lesions, overall survival and safety as the secondary outcomes. Further, researchers examined the relationship between baseline Expanded Disability Status Scale (EDSS) scores and the evolution of the same over time.
Results showed 62 patients had relapsing-remitting MS, eight had secondary progressive MS and two had primary progressive MS, with follow-up ranging between 8 months and 20 years. During the follow-up period, Brunet and colleagues reported no new relapse. They noted there were 206 relapses, or 1.1 relapses per patient per year, pre-transplant, with 195.9 patient-years of follow-up. Further, they noted zero relapses post-transplant, with 288 patient-years of follow-up. No patient received another form of disease modifying treatment.
Brunet and colleagues reported one death 27 days after aHSCT due to sepsis and veno-occlusive disease of the liver. One other patient died of pneumonia 67 months after aHSCT. Although MRI scans were not performed regularly during follow-up, no new lesions were reported post-transplant. Patients with a lower baseline EDSS score more often had EDSS reductions post-transplant. Among 26 patients with baseline EDSS less than five, 13 had improvements in EDSS scores vs. six with a baseline EDSS greater than or equal to five.
“Bone marrow transplant is effective for patients who are adequately selected, and the key is to try to identify which patient will be the best candidate,” Brunet said. “If you have a patient who failed the standard DMT, think about the transplant and evaluate the patient and see if they will have the best outcome or not depending on their situation.”
Biohellenika today renewed its license as a Umbilical Cord Blood Bank in accordance with the new Terms and Conditions and the intention of the Ministry of Health to complete the procedures for those banks that meet the requirements.
Respecting the decision of the parents to keep the stem cells of their children, Biohellenika took care to offer them the most complete and quality services. For this reason it recently renewed its international accreditation from AABB (American Association of Blood Banks) and has proceeded to the second international accreditation by FACT NetCord. This second accreditation is expected to be completed in the next two years.
It also has the most complete accreditation system by the ESYD (National Accreditation System), which includes all the tests required for the storage of stem cells, according to the Terms and Conditions.
At the same time it perfects the GMP system (good practice) of laboratories for the production of cell therapy products.
Biohellenika has a strong Research and Development Department and a strong medical team, which can support clinical trials using stem cells for serious diseases.
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