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Biohellenika is always present in innovation

Biohellenika attends 70th Congress of the Greek Society of Biochemistry and Molecular Biology

Biohellenika won another distinction at the 70th congress of the Greek Society of Biochemistry and Molecular Biology in Athens on 29/11/2019-2/12/2019.

The Research &Development Department of Biohellenika has for the first time developed an innovative system of combined application of adipose tissue stem cells and time-controlled release of anti-angiogenic drugs by nanofibers with the aim of addressing retinopaties. There are no effective treatments for retinal diseases as most of them delay the onset of clinical symptoms rather to reverse the main pathophysiology of the disease. For this reason most of the patients and to blindness. The only promising treatment today are cellular therapies using stem cells. However, limitations related to the pathological  environment in the diseased tissue make it difficult to  provide such forms of the treatment.

For the first time we propose in this study a system of gradual reduction of abnormal neovascularization in the retina using specially constructed biomaterials carrying ant-angiogenic agents accompanied by adipose tissue stem cells administration. The combination therapy we propose is already being in animal models of induced retinal damage.

 

15th of Novemer is  dedicated to Placenta-Cord Blood

Placenta-cord blood can save lives.  Expecting parents mut be informed about the current and future use of cord blood stem cells and decide for family use or for public donation.   

https://parentsguidecordblood.org/en/news/cerebral-palsy-expanded-access-program-europe

Cerebral Palsy Expanded Access Program in Europe November 2019 Frances Verter, PhD   Cerebral Palsy patients and families living in Europe now have expanded access to a program of therapy with cord blood stem cells. The new program is open to children that have a diagnosis of cerebral palsy and also have their own cord blood in storage. Patients that meet these conditions can receive cord blood stem cell therapy in a hospital in Poland. The fact that the program is “expanded access” means it is not a clinical trial with strict criteria to participate and limited enrollment. Over time it should be possible to treat hundreds of patients. This is a big advance for these children and their families, when until now there was no such program on the European continent. The term “expanded access” comes from the FDA in the United States, where it is used to describe programs that enable patients with a “serious” disease or condition to gain access to an “investigational medical product”, one that has been proven safe but the efficacy is still under study, when there is no comparable or satisfactory alternative therapy. The first expanded access program (EAP) of cord blood stem cell therapy for cerebral palsy launched in the United States at Duke University in Oct. 2017, under FDA registration as clinical trial NCT03327467. At the Cord Blood Association annual meeting in Sept 2019, Dr. Joanne Kurtzberg of Duke stated in her talk that to date over 320 children have received treatment through this program.

Research on Allogeneic Cord Blood for Stroke

 September 2019 by Frances Verter, PhD  

The possibility of using cord blood stem cells to treat adult stroke patients is an area of research that holds enormous potential. Stroke affects one in every six people worldwide, and is the world’s second most common cause of death1-3. The definition of a stroke is the sudden death of brain cells due to lack of oxygen, which happens when blood flow is disrupted in a region of the brain. In about 87% of strokes, the blood flow is disrupted by a blockage, and this is called an ischemic stroke, but stroke can also be caused by bleeding in the brain, and this is called hemorrhagic stroke. Stem cell therapies emerged as a paradigm for stroke about a decade ago. Contrary to long-held beliefs, we now know that the brain can recover to some extent after injury, and stem cell therapy offers a potential for multimodal repair mechanisms. “Immediately after stroke, several events, including edema, deafferentation, and inflammation, occur around the infarct, and some early functional recovery can be attributed to the resolution of edema and inflammation. However, this is usually limited, and other processes, including immunomodulation, angiogenesis, endogenous neurogenesis, and altered gene expression, may be involved in the longer-term recovery of function”. According to the resource CellTrials.org, over the period from January 2018 through July 2019, 77 clinical trials have been registered worldwide to treat stroke with cell therapy, with 68% of the trials listed on ClinicalTrials.gov and 32% listed in 9 other trial registries. The most common source for cells used in stroke cell therapy is bone marrow, at 43% of these 77 trials.  Some stroke therapies developed from bone marrow have a strong pipeline of development and are close to approval in their respective countries. The most common cell type used in stroke cell therapy is mesenchymal stem/stromal cells (MSC). The other common group is mononuclear cells (MNC) from a blood-based source comprise 35% of these trials. Stroke therapy with cord blood MNC make up 17% of the total trials. Cord blood is emerging as a serious competitor in cell therapy for stroke. The main reason is because MNC from cord blood trigger less graft-versus–host reaction than adult sources of MNC. Since 2011, every single stroke trial that sourced MNC from bone marrow or peripheral blood relied on autologous cells, where the patient had to undergo a harvest of his or her own cells. A recent trend is for stroke therapy with cord blood cells to push against the envelope of HLA matching. In March 2015, Duke University embarked on a novel phase 1 trial NCT02397018 to test the safety of treating stroke patients with an infusion of cord blood that was completely unmatched except for standard ABO blood typing. Ten patients between ages 45 and 79 that had suffered an ischemic stroke received intravenous infusions within 3 to 10 days after the stroke, and no adverse events related to the therapy were noted. The results from this trial were published in May 20 189. Currently, Duke and collaborators are running a larger phase 2 double-blind trial NCT03004976 at 6 medical centers with the target enrollment of treating 100 patients by March 2020. There are other notable examples of cord blood trials for stroke. The hybrid cord blood bank StemCyte has supported trials NCT01673932 in Hong Kong and NCT02433509 in Taiwan that treated patients with allogeneic cord blood having a minimum 4 out of 6 HLA match. In South Korea, the research center at Bundang CHA Hospital ran trial NCT01884155 in 2013, and in July 2019 they registered a phase 2 trial NCT04013646 that will treat stroke patients with allogeneic cord blood having a minimum 3 out of 6 HLA match. Also in July 2019, the for-profit clinic Blue Horizon International posted ISRCTN10678357 on the WHO trial registry, stating that they had a registry of 97 stroke patients treated in China with cord blood that only had ABO blood type match. If clinical trials of allogeneic cord blood therapy for stroke continue to meet their endpoints, this could be an exciting new application for donated cord blood.  In the United States, about 795,000 people suffer a stroke each year, and 140,000 are fatal1-3. If only 1% of these patients received cell therapy, that would be comparable to the total number of allogeneic stem cell transplants per year in the United States. Ultimately, a successful cord blood therapy will find itself in competition against cell therapy products for stroke that are already near approval.  The possibility to utilize cord blood cells as an “off-the-shelf” product (actually out of the cryogenic freezer) with no HLA matching would make cord blood more competitive against other cell therapies that are based on MSC and operate as universal donor products. Regardless of how the research on allogeneic cord blood for stroke evolves, it promises to be an exciting topic to follow. https://parentsguidecordblood.org/en/news/research-allogeneic-cord-blood-stroke

Creating a Savior Child August 2019 by Liat Ben-Senior,

 When parents have a child with a serious illness, they face heart-wrenching treatment decisions. For those families with a child that requires a stem cell transplant, often there is the additional hurdle of finding a donor for the transplant. A successful transplant requires an HLA match between donor and recipient. However, the probability of finding a suitable match among family members is only 30% overall. Among siblings, the chances of having a perfect HLA match range from 13% to 51% in the United States, depending on patient age and ethnicity. If members of the family do not match, the next options are to seek a match from the registries of unrelated adult donors, or from a registry of donated cord blood. But another factor parents need to consider, is that stem cell transplants have fewer complications and better survival rates with donors who are not just a match on the HLA types, but who are related to the patient. Given these considerations, some parents explore the possibility of conceiving another child that will be an HLA match to their sick child. This is often called a “Savior Sibling”. When the savior child is born, its umbilical cord blood can be saved as a source of stem cells for the patient in need of a transplant. Creating a savior child is not so simple as just getting pregnant and hoping for the best. The natural chances that another baby will be an exact HLA match to an older sibling are only 25%. Moreover, if the sick child has a hereditary disease, it is important to ensure that the next child does not inherit the genes that carry it. What is Preimplantation Testing? Preimplantation Genetic Testing (PGT) refers to the genetic profiling of embryos. It is used to screen embryos for genetic diseases or chromosomal abnormalities. First the parents must conceive embryos through in-vitro fertilization (IVF) procedures. From each embryo, PGT takes a biopsy of only a few cells and conducts a genetic analysis. This analysis can search to exclude embryos carrying a genetic variant that causes a hereditary disease, and it can search to find embryos that are an HLA match to a sibling. Preimplantation genetic testing can be considered as a form of prenatal diagnosis. Preimplantation genetic testing was first introduced in 1990 by selecting female embryos to prevent the birth of male patients affected with X-linked recessive disorders. The PGT allows diagnosis at three levels: chromosome abnormalities/aneuploidy (PGT-A), structural chromosomal abnormalities (PGT-SR), and single gene diagnosis and HLA typing (PGT-M). Many fertility clinics are now offering PGT testing as a tool to improve IVF outcomes, to avoid the occurrence of known lethal or severely disabling inherited genetic diseases, and also as a way to avoid recurrent implantation or pregnancy failures. Preimplantation genetic testing offers parents a way to ensure their children will not be affected by a genetic disorder without facing the risk and consequences of terminating the pregnancy. Foundation. https://parentsguidecordblood.org/en/news/creating-savior-child

 

Mesenchymal stem cells collected from the cord tissue loose their stemness after prolonged  culture, according to the below publication. So we must collect the mesenchymal stem cells from the whole length  of the cord and do not cryopreserve the cord in pieces,  without previous extraction of the cells.  Proliferation of the cells  to reach the appropriate number of cells, according to the weight of the patient, does not be safe and effective for therapies. 

Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions  

WEICHAO Zhai,DERRICK YONG,JEHAN JOMAA EL-JAWHARI, RICHARD CUTHBERTDENNIS MCGONAGLE,MAY WIN NAING. ELENA JONESDOI:  https://doi.org/10.1016/j.jcyt.2019.05.001

Regardless of their tissue of origin, multipotent mesenchymal stromal cells (MSCs) are commonly expanded in vitro for several population doublings to achieve a sufficient number of cells for therapy. Prolonged MSC expansion has been shown to result in phenotypical, morphological and gene expression changes in MSCs, which ultimately lead to the state of senescence. The presence of senescent cells in therapeutic MSC batches is undesirable because it reduces their viability, differentiation potential and trophic capabilities. Additionally, senescent cells acquire senescence-activated secretory phenotype, which may not only induce apoptosis in the neighboring host cells following MSC transplantation, but also trigger local inflammatory reactions. This review outlines the current and promising new methodologies for the identification of senescent cells in MSC cultures, with a particular emphasis on non-destructive and label-free methodologies. Technologies allowing identification of individual senescent cells, based on new surface markers, offer potential advantage for targeted senescent cell removal using new-generation senolytic agents, and subsequent production of therapeutic MSC batches fully devoid of senescent cells. Methods or a combination of methods that are non-destructive and label-free, for example, involving cell size and spectroscopic measurements, could be the best way forward because they do not modify the cells of interest, thus maximizing the final output of therapeutic-grade MSC cultures. The further incorporation of machine learning methods has also recently shown promise in facilitating, automating and enhancing the analysis of these measured data.

Key Words:

label-freemultipotent mesenchymal stromal cellsnon-destructivereplicative agingsenescence

 

Identification of senescent cells in multipotent mesenchymal stromal cell cultures: Current methods and future directions

WEICHAO Zhai,DERRICK YONG,JEHAN JOMAA EL-JAWHARI, RICHARD CUTHBERT

DENNIS MCGONAGLE,MAY WIN NAING. ELENA JONESDOI: https://doi.org/10.1016/j.jcyt.2019.05.001

Abstract

Regardless of their tissue of origin, multipotent mesenchymal stromal cells (MSCs) are commonly expanded in vitro for several population doublings to achieve a sufficient number of cells for therapy. Prolonged MSC expansion has been shown to result in phenotypical, morphological and gene expression changes in MSCs, which ultimately lead to the state of senescence. The presence of senescent cells in therapeutic MSC batches is undesirable because it reduces their viability, differentiation potential and trophic capabilities. Additionally, senescent cells acquire senescence-activated secretory phenotype, which may not only induce apoptosis in the neighboring host cells following MSC transplantation, but also trigger local inflammatory reactions. This review outlines the current and promising new methodologies for the identification of senescent cells in MSC cultures, with a particular emphasis on non-destructive and label-free methodologies. Technologies allowing identification of individual senescent cells, based on new surface markers, offer potential advantage for targeted senescent cell removal using new-generation senolytic agents, and subsequent production of therapeutic MSC batches fully devoid of senescent cells. Methods or a combination of methods that are non-destructive and label-free, for example, involving cell size and spectroscopic measurements, could be the best way forward because they do not modify the cells of interest, thus maximizing the final output of therapeutic-grade MSC cultures. The further incorporation of machine learning methods has also recently shown promise in facilitating, automating and enhancing the analysis of these measured data.

Key Words:

label-freemultipotent mesenchymal stromal cellsnon-destructivereplicative agingsenescence

 

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