Nobody enjoys getting their blood drawn. It might be painless and quick for some but there are times that waiting in lines can take hours along with rare instances where the nurse drawing blood has to poke several times before finding a vein to draw from. If the latter has ever happened to you then fear no more.

The tasso company in the United States have developed a device known as Hemolink that will replace painful needles to make blood testing easy and much more convenient. The ice cube sized device allows patients to self-administer a blood test in as little as 2 minutes.

The device does not require puncturing the skin into a blood vein and can be used by simply placing the device against the skin to creates a vacuum effect causing blood to be pulled blood via microscopic capillaries. The Hemolink device is disposable and is made up of only six molded parts made of plastic which will also simplify the manufacturing process while cuttings costs. The device is currently designed to extract about .15 cubic cm of blood which is enough for most lab panels including: blood sugar tests, cancer cell tests, cholesterol tests and infection markers.

Current blood tests are also cumbersome as they need to be stored at specific temperatures in a process known as “cold-chain.” This means that each step of the blood sampling must also be regulated to ensure the blood samples all stay at the same temperature to allow for correct results.

The new Hemolink device will permit users to store blood samples for up to 7 days at maximum temperatures of 60 degrees Celsius or 140 degrees Fahrenheit. This user-friendly device will enable almost anyone to take and send blood samples in to a lab for analysis without the need of dry ice rush-deliveries.

The most likely users will be people who need to test semi-frequently to monitor active cancers,Autoimmune diseases like ulcerative colitis, Diabetes 2, or vascular conditions like heart disease. The low cost device will help replace expensive machines and additional staff as the tests are 100% non-invasive and can be performed in the comforts on the home environment.

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Science is a tribute to what we can know although we are fallible. – Jacob Bronowski

Biologist Dr Haruko Obokata of the RIKEN institute in Kobe Japan has been unable to reproduce pluripotent results from a controversial “Acid Bath” technique involving mice derived adult stem cells. The technique was coined STAP or “stimulus-triggered acquisition of pluripotency” and made international headlines earlier in 2014 with a stunningly simple method of reverting cells to Pluripotency.[3] STAP cells should be able to differentiate themselves into placental cell stage which would make even more useful (clinically) as embryonic cells or even iPS cells (induced pluripotent stemcells) which were previously thought to be the most powerful cell types due to their abilities to transform themselves into nearly every cell type in the human body.[2] The value of such cells in regenerative medicine would be unimaginable.

STAP cells and spontaneous pluripotency was first hypothesised in 2003 by Martin and Charles Vacanti. Dr Obokata learned about STAP cells while studying under Dr Charles Vacanti at Harvard medical school.

A breakthrough was first noted by Dr Yoshiki Sasai and Obokata in 2013 though their experiments that subjected adult stem cells to extremely stressful environments, such as bacterial toxins,extreme physical pressure through the use of a capillary tubes and exposing the common cells to a mild acidic bath. [1] The cells were then engineered to glow fluorescent green to express the genes that are prevalent in pluripotent cells. The research papers that Dr Obokata co-authored were published in the Journal “Nature” in January of 2014 rapidly gaining worldwide headlines.

Many scientists in the international community quickly attacked the credibility of the findings by claiming the images were digitally enhanced and perhaps not authentic. Upon further investigation, the RIKEN centre found evidence of scientific misconduct resulting in a retraction of the published paper. Upon the retraction of the paper, the co-author Dr Yoshiki Sasai committed suicide at the RIKEN institute.

The RIKEN institute had allowed the remaining author ( Dr Haruko) 3 months (until the end of November of 2014) to reproduce the results and validate the original findings.

After performing rigorous testing on the technique, the results could not be replicated. The scientists even tried to introduce the STAP cells to an embryo of a mouse to see if it would contribute to the creation of various tissues but were unsuccessful in their findings.

On Dec 19th 2014, Dr Haruko Obokata resigned from her position at the RIKEN Center and posted her resignation letter on RIKEN’s website along with the results from the organization’s’ internal investigation.

In the end the systematic methodology of science did what it is supposed to do. Scientists and researchers create experiments and then conduct trials. If their results are interesting, they get published in the public realm. Since the results are now public, other scientists and researchers can/should try to reproduce the findings to verify their authenticity. If the subsequent results are verified independently they become stronger, however if the results cannot be replicated, the findings were incorrect and there must have been a mistake somewhere in the process.

Unfortunately, in today’s world the media and press try to label all findings as scientific truth without realising that even published papers can be incorrect at times in our eternal pursuit of biological answers.

Published Clinical Citations

• [1] ^ Obokata, Haruko, Teruhiko Wakayama, Yoshiki Sasai, Koji Kojima, Martin P Vacanti, Hitoshi Niwa, Masayuki Yamato, and Charles A Vacanti. 2014. Stimulus-triggered fate conversion of somatic cells into pluripotency. Nature, no. 7485 ( 30). doi:10.1038/nature12968. https://www.ncbi.nlm.nih.gov/pubmed/24476887

• [2] ^ Pera, Martin F. 2014. Stress management: a new path to pluripotency. Cell stem cell, no. 3 ( 6). doi:10.1016/j.stem.2014.02.009. https://www.ncbi.nlm.nih.gov/pubmed/24607402

• [3] ^ Obokata, Haruko, Yoshiki Sasai, Hitoshi Niwa, Mitsutaka Kadota, Munazah Andrabi, Nozomu Takata, Mikiko Tokoro, et al. 2014. Bidirectional developmental potential in reprogrammed cells with acquired pluripotency. Nature, no. 7485 ( 30). doi:10.1038/nature12969. https://www.ncbi.nlm.nih.gov/pubmed/24476891

There are generally 2 ways that human cells can die:

1. They are destroyed through an injury or viral agent
2. The cells induce themselves to commit suicide

Cell Death through Injury or Harmful agents

Cells in our bodies that have been damaged due to injuries, such as exposure to lethal/toxic chemicals or mechanical damage tend to go through a series of changes before they die. The cells tend to swell up and eventually the contents of the cells leak out of the membrane leading to immediate inflammation of the tissues surrounding the cell.

Apoptosis Animation Video

Death by programmed suicide

Cells can also be induced/naturally programmed to commit suicide for normal cell turnover and to allow new healthy cells to flourish. The PCD phase starts but the cells shrinking and developing tiny bubble like markers on the surface. After that the DNA & Proteins (chromatin)in the cell nucleus degrades enough to release cytochrome c that breaks down the cells further until the release of UTP and ATP.

These ATP and UTP nucleotides then bind to the receptors of phagocyte cells such (dendritic cells and macrophages) to help attract themselves to the dying cell. Phospholipid phosphatidylserine then gets exposed to surface creating an “eat me” signal on the phagocytes that devour the remaining cell fragments. These phagocyte cells slowly secrete cytokines IL-10 and TGF-β which inhibits inflammation.

The series of linear events that occur in the suicidal death is so orderly that scientists refer to the process as PCD or programmed cell death. The function of programmed cell death is as intrinsic to our cells the process of mitosis or meiosis.  The cycle of a programmed cell death is known as cell apoptosis. (pronounced APE oh TOE sis)

Why do cells commit suicide?

Cells commit suicide for two different reasons.

1. Programmed cell death or PCD is needed for natural development. A good example is the formation of our toes and fingers in the fetus that requires nature to use apoptosis to remove some tissue between the fingers and toes to allow for proper function. Another example is in the formation of synapses (signals) between neural cells that require any excess or surplus cells get eliminated through the process of apoptosis.
2. PCD is also needed to naturally destroy cells if the body recognizes them as a threat to our system or to maintain the overall integrity of an organism. A good example of Apoptosis is when our cells get infected with a virus. Our body will choose to kill the damaged cells and save the surrounding tissues.

It is believed that defects in our apoptotic process is associated with certain autoimmune conditions such as crohn’s disease, lupus and/or rheumatoid arthritis. Other occurrences of Apoptosis occurs in Cells with DNA or genome damage that may cause disruption in proper embryonic development thus leading the child to birth defects or to stop from becoming cancerous.

Some types of radiation and chemicals that are used in cancer therapies also help to induce apoptosis for some types of cancer cells in the hopes of containment.The survival of our cells requires that it receive constant positive stimulation from surrounding cells. Some well known examples of positive signalling comes from growth factors for neuron cells and Interleukin-2 which is an essential factor needed for mitosis of lymphocytes

On the other side of the spectrum,the receipt of negative signals from cells can also lead to apoptosis of sensory motor neurons. Increasing levels of oxidants inside the cells can cause damage to our DNA.[1] Other negative signals include:

• X-rays
• Ultraviolet lights “UV”
• Chemotherapy drugs
• Rapid Accumulation of proteins

When these negative signals occur, molecules will begin to bind to the cell surface receptors and natural signal the cells to begin the apoptosis cycle.

Examples of cell death activators include:

• Lymphotoxin or TNF-β
• Tumor necrosis factor-alpha or TNF-α
• Fas ligand or FasL

The 3 Primary Mechanisms of Cell Apoptosis

A Cell commits suicide by apoptosis using 3 types of mechanisms:

1. Internal signals (mitochondrial pathway)
2. External signals (death receptor pathway)
3. Apoptosis-Inducing Factor or AIF [2]

Cancer and Apoptosis

Some viruses that are associated with cancer can use biological trickery to prevent the natural cycle of apoptosis in the cells they have invaded. Examples include the human papilloma viruses or HPV that has been known to cause cervical cancer. The Epstein-Barr Virus or EBV is another example of cell trickery and is associated with some types of lymphomas and can also cause mononucleosis.

Apoptosis in our Immune System

The primary function of our immune system us to respond and protect our bodies from foreign invaders through the proliferation of lymphocyte cells (T and/or B cells). After our systems have been protected and the job is done, the cells must be removed to allow the healing process. This removal of cells is done through the process of apoptosis.

Apoptosis Vs Necrosis

The opposite of apoptotic cell death is known as cell necrosis. Necrosis is considered a toxic process in our bodies where the cells become passive victims. Necrosis generally refers to the natural or “un-programmed” degradative processes that occurs after cell death. Many scientists do not like to use the term necrosis to describe cell death.[3]

Oncosis the term that is used to describe the process of events that lead to necrosis. In necrosis, cell swelling and karyolysis occur compared to apoptosis which causes death through pyknosis, karyorrhexis and cell shrinkage. The medical terms “oncotic necrosis” or “oncotic cell death” are sometimes used to describe programmed cell death that is followed up by by cell swelling,[4]

Natures ability to control the life & death of cells has tremendous therapeutic potential in regenerative medicine. Its crucial that we understand when Inappropriate apoptosis occurs as it plays a vital factor in many medical conditions such as neurodegenerative brain diseases such as ALS,Motor Neuron Disease, ischemic heart disease, cancers and many types of autoimmune disorders. The stem cell regeneration center will continue to publish the latest findings, advancements and clinical trials to the benefit all patients across the world.

To learn more about our Apoptosis and how programmed cell death plays a role in medical treatments and therapies please contact us today.

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Published Clinical Citations

• [1] ^ Ekchariyawat, Peeraya, Arunee Thitithanyanont, Stitaya Sirisinha, and Pongsak Utaisincharoen. 2013. Involvement of GRIM-19 in apoptosis induced in H5N1 virus-infected human macrophages. Innate immunity, no. 6 (March 25). doi:10.1177/1753425913479149. https://www.ncbi.nlm.nih.gov/pubmed/23529854

• [2] ^ Kheansaard, Wasinee, Prapaporn Panichob, Suthat Fucharoen, and Dalina I Tanyong. 2011. Cytokine-induced apoptosis of beta-thalassemia/hemoglobin E erythroid progenitor cells via nitric oxide-mediated process in vitro. Acta haematologica, no. 4 (September 21). doi:10.1159/000329903. https://www.ncbi.nlm.nih.gov/pubmed/21934298

• [3] ^ Kumar, Sunil, Anup Singh Pathania, A K Saxena, R A Vishwakarma, Asif Ali, and Shashi Bhushan. 2013. The anticancer potential of flavonoids isolated from the stem bark of Erythrina suberosa through induction of apoptosis and inhibition of STAT signaling pathway in human leukemia HL-60 cells. Chemico-biological interactions, no. 2 (July 9). doi:10.1016/j.cbi.2013.06.020. https://www.ncbi.nlm.nih.gov/pubmed/23850732

• [4] ^ Yorsangsukkamol, Juthaporn, Angkana Chaiprasert, Tanapat Palaga, Therdsak Prammananan, Kiatichai Faksri, Prasit Palittapongarnpim, and Narapon Prayoonwiwat. 2011. Apoptosis, production of MMP9, VEGF, TNF-alpha and intracellular growth of M. tuberculosis for different genotypes and different pks5/1 genes. Asian Pacific journal of allergy and immunology, no. 3. https://www.ncbi.nlm.nih.gov/pubmed/22053594

UPDATED July 06, 2020 Human Endothelial cells “EC” are estimated to account for nearly 1 kg of mass in the human body. This mass is about the same as our livers. Endothelial cells are thought to be produced by the splanchnopleuric mesoderm. These vital cells line the insides of all our blood vessels, including microscopic capillaries to larger arteries such as the aorta. The Endothelial cells help create a one-cell-layer (thickness) known as the endothelium. The endothelium can be found on the walls of a heart chamber and also on the carriers of blood plasma through the human body known as lymphatic vessels. In large blood vessels like arteries and veins, the endothelium layer forms thicker layers of fibers and muscle cells that are essential to our abilities to survive and function properly.[1]

Endothelial Cells Overview – VIDEO

Endothelial Cells “ECs” & The Blood Brain Barrier

The primary purpose of ECs is to help provide a safety barrier between our bodily tissues and blood. For our bodies to function properly, our blood must be contained safely inside a transporting lane, that allows certain proteins and chemical substances to move in and out of the blood vessels in a safe and controlled manner. Our endothelium is the perfect layer for such a task. It helps provide a selectively permeable layer (filter) in the blood vessel system that allows certain white blood cells and/or chemicals to move freely around in our bodies to go where they need to go without restriction.[2]

The primary role of the endothelium as a protecting barrier is especially critical around the neural pathways. Our endothelial cells are also part of blood-brain barrier “BBB.” The blood brain barrier is a thin layer that helps to separate flowing blood flowing vessels around the brain from our brain tissue, cerebrospinal fluid and neurons.

Epithelial Cells vs Endothelial cells

Epithelial cells are usually found coated around the inner surface of our internal organs where Endothelial cells are usually found lined in the interior surfaces of blood vessels. Our endothelial cells act very much like a sieve or filter, that restricts the passage of larger molecules,bacteria or toxic substances into our brain tissue while allowing the necessary molecules such as hormones, oxygen,cytokines and enzymes to pass safely and without restriction. The filtering function also allow waste like carbon dioxide (produced by our neurons) to easily diffuse out of our brains and back into our bloodstream for disposal.[3]

Endothelial stem cells or “ESC” are one of 3 types of adult stem cells that are found in our bone marrow. EDCs are multipotent, which means that they have the distinct ability to give “birth” to many type of cells. This is slightly different than pluripotent cells which can give “birth” to nearly all types of cells in the human body. Like stem cells, endothelial cells can also self-renew and differentiate. Endothelial stem cells help form progenitor cells, that basically act like intermediate stem cells and lose their potency. Progenitor cells are locked from being able to further differentiate. Endothelial stem cells eventually produce endothelial cells “EC”, which then form to create the thinly-walled endothelium layer that line the inner surfaces of our blood and lymphatic vessels.

Endothelial progenitor cells “EPC” are a small population of rare and unique cells that are constantly circulating in the blood vessels and have the unique capacity to differentiate into endothelial cells that help to make the lining of all our blood vessels. Vasculogenesis is the natural process where blood vessels are created in our bodies from endothelial progenitor cells.

Endothelial progenitor cells also participate in pathologic angiogenesis such as that found in retinopathy and tumor growth. Endothelial progenitor cells are also very important in tumour growths and are vital for the process of angiogenesis and metastasis. Various growth factors,cytokines and hormones can cause hematopoietic and endothelial progenitor cells to be mobilised into our peripheral blood circulation system ultimately leading to blood vessel formation. At the regeneration center, Endothelial progenitor cells are usually marked and identified in stem cell therapies using a flow cytometer.

To learn more about Endothelial progenitor cells or if you have any other questions please contact us today.

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Published Clinical Citations

• [1] ^ Busse, R. & Fleming, I. Vascular endothelium and blood flow. Handb. Exp. Physiol. 176, 43–78 (2006)

• [2] ^ Minshall, R. D. & Malik, A. B. Transport across the endothelium: regulation of endothelial permeability. Handb. Exp. Pharmacol. 176, 107–144 (2006)

• [3] ^ Aird, W. C. Phenotypic heterogeneity of the endothelium: I. Structure, function and mechanisms. Circ. Res. 100, 158–173 (2007) https://www.ahajournals.org/doi/full/10.1161/01.res.0000255691.76142.4a

G-CSF Stimulation use in Stem Cell Therapies

Granulocyte-colony stimulating factor is also known as colony-stimulating factor 3,G-CSF, GCSF, GM-CSF or Rm-GSF.Granulocyte Colony-Stimulating Factors are a special kind of protein or “growth factor” that the body naturally manufactures in the bone marrow that is often used in cancer treatments such as chemotherapy and NK Cell Therapy.

Creating White Blood Cells – VIDEO

G-CSF’s have the ability to promote bone marrow stimulation for it to produce white blood cells “WBC” by increasing its numbers within a short span of time. There are three main types of G-CSF including:

• Filgrastim
• Pegylated filgrastim
• Lenograstim.

The side effects of Chemotherapy greatly compromises a humans health in the sense that the radiation significantly lowers our bodies defense mechanism thanks to the reduction in neutropenia or White Blood Count leading to the decreased resistance to viruses and infections. This is where the G-CSF comes into play, as it can be used to increase the total WBC count. Granulocyte Colony-Stimulating Factors are also sometimes used before autologous stem cell therapy that requires use of Bone marrow cells or stem cells from the peripheral blood.

When you undergo chemotherapy, the reduction in white blood cell is usually temporary during treatment, and often normalizes naturally before each round of chemotherapy. However, for some patients with severely compromised health, the succeeding dosage of chemo must be reduced or postponed if the if the G-CSF count does not recover as it may put the patient at additional risk.

Given this predicament, the G-CSF encourages the production of more WBC and eventually increases your resistance to infection. However, it does not necessarily mean that every chemotherapy session needs G-CSF integration. If patients are recovering naturally and are able to produce enough white blood cells, then G-CSF stimulation will not be needed.

Speed Up Production of Stem Cells

In cases of chemotherapy requiring high dosages, G-CSF will have to be incorporated to stimulate the production of bone marrow and the eventual production of stem cells. The Regeneration Center of Thailand uses G-CSF stimulation in some treatment protocols to allow stem cell populations to be produced rapidly via the bone marrow, collected, and then banked to be eventually used in a treatment.

G-CSF is generally administered subcutaneously via injection usually several days before stem cell transplants or several days after chemotherapy. It is supposed to be dispensed on a daily basis, but the number of injections would really depend upon the patients condition and the type of G-CSF used. For instance, in the case of pegylated filgrastim, since this can stay in the body for a longer period, it can be administered only once after every chemotherapy cycle.

Side Effects & Risks of Granulocyte Colony-Stimulating

Since our body is a natural producer of G-CSF, when injected, the amount of circulating G-CSF typically goes above the normal ranges found. Some of the side effects noted with G-CSF Stimulation are dull pain or discomfort in the bony areas such as the extremities, pelvis, and back. Other symptoms include skin itchiness,fevers, chills, and edema or fluid retention. These effects are usually temporary and disappear after a few days.

To learn more about our G-CSF and its use in our treatment protocols please contact us today.

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UPDATED July 06, 2020 The human spinal cord,skeleton cells and muscle cells are all created from cells known as NMP’s or neuro-mesodermal progenitors. The formation of these vital cells has remained a mystery until now. These cells are created in a complex yet carefully timed signal by a growing embryo which instructs the neuro-mesodermal progenitor cells to differentiate into the various types of cells needed for our musculoskeletal system.

Cinderella Stem Cells

In the past, researchers have been able to differentiate cells into muscle,skin,nerve and bone cells from stem cells in the laboratory but they have not been able to create the NMP cells in the past. Stem cell researchers currently have the capability to grow liver, heart and brain tissue in the lab environment but never NMP cells despite the fact that NMP’s were first discovered over 100 years ago.

NMPs were regarded as very mysterious thereby earning the name of “Cinderella cells.” These cells are significant because they are the source of our spinal cord and are found in the majority bones and muscle tissues in our bodies.

The ability to recreate these cells in the lab will result in much better functioning cells as opposed to previous experiments that forced the creation of NMP cells directly from stem cells. By mimicking nature researchers are able to create cells that bear a much closer resemblance to naturally created bone,muscle and nerve cells.

The creation of these “intermediate” NMP cell has not been possible until now. To create the NMP cells,researchers at the MRC National Institute for Medical Research at the University of Edinburgh carefully examined then imitated the natural process in a petri dish, differentiation mice cells at first then human stem cells into becoming functioning NMP cells that eventually formed into spinal cord cells.

The breakthrough came when researchers found a way to trick the stem cells into this intermediate stage cell before turning them into fully functioning muscle and spinal cord cells.

The researchers also noted that the discovery is an important step in the right direction as they continue to investigate all the potential paths and pitfalls associated with this particular type of cell. In-depth knowledge of the early developmental stage of NMP cells will probably play a significant role in supplying future researchers knowledge on how to better treat patients with partial or full paralysis due to spinal cord injuries or Traumatic brain injuries.

To learn more about Neuro-Mesodermal Progenitor Cells please contact us today.

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