Induced Pluripotent Stem Cells | iPS | iPSCs | hiPSCs

Induced pluripotent stem cells or iPS cells are also known as IPSCs are a recent discovery and like STAP cells, have the potential to revolutionise regenerative medicine in the world. The IPS cells are lab created cells with the power to differentiate as great as the embryonic stem cell lines. In 2006, scientists identified four key genes in embryonic stemcells that empowered them to regenerate and differentiate into distinct kinds of somatic cells. Scientists essentially took skin cells and reprogrammed them into iPS cells.[1]

What are iPS Cells? – VID

IPSCs cells share many features with embryonic stem cells. These completely transformed cells can be distinguished from ES cells using SIRT1. SIRT1 also helps ensure the integrity of the genome of stem cells that come from the cell reprogramming procedure. The first human trials of induced pluripotent stem cells took place on six people who had age-related macular degeneration (AMD) . Embryonic cells were induced into pluripotent stem cells using plasmid DNA. An induced pluripotent stem (iPS) cell can be grown from virtually any tissue in any human (old or young) and is genetically altered to behave similar to that of embryonic cells.[2] Induced pluripotent cells (iPS cells) were at one stage “non-pluripotent” cells. Human induced pluripotent stem cells (hiPSCs) and hESCs or human embryonic stem cells for IVF and cryo cell banking were previously the primary sources for mesenchymal cells that were used in regenerative medicine at the regen center of Thailand.

The Basic Types of Stem Cells

Another way to generate embryonic stem cells and induced pluripotent stem cells is from somatic cell nuclear transfer (SCNT).[3] DnA or biological substance must be donated from living donors. Induced Pluripotent Stem Cells or iPSCs are converted into adult cells through genetic engineering techniques that introduce pluripotent genes into the adult cells to be used for neurodegenerative illnesses like ALS,Brain Injuries, Ataxia disease and Spinal cord damage and in treating heart disease and CHF therapy.

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Published Clinical Citations

  • [1] ^ Noisa, Parinya, Carina Lund, Kartiek Kanduri, Riikka Lund, Harri Lähdesmäki, Riitta Lahesmaa, Karolina Lundin, et al. 2014. Notch signaling regulates the differentiation of neural crest from human pluripotent stem cells. Journal of cell science, no. Pt 9 (February 25). doi:10.1242/jcs.145755. https://www.ncbi.nlm.nih.gov/pubmed/24569875

  • [2] ^ Prè, Deborah, Michael W Nestor, Andrew A Sproul, Samson Jacob, Peter Koppensteiner, Vorapin Chinchalongporn, Matthew Zimmer, Ai Yamamoto, Scott A Noggle, and Ottavio Arancio. 2014. A time course analysis of the electrophysiological properties of neurons differentiated from human induced pluripotent stem cells (iPSCs). PloS one, no. 7 (July 29). doi:10.1371/journal.pone.0103418. https://www.ncbi.nlm.nih.gov/pubmed/25072157

  • [3] ^ Tubsuwan, Alisa, Soumeya Abed, Annette Deichmann, Melanie D Kardel, Cynthia Bartholomä, Alice Cheung, Olivier Negre, et al. 2013. Parallel assessment of globin lentiviral transfer in induced pluripotent stem cells and adult hematopoietic stem cells derived from the same transplanted β-thalassemia patient. Stem cells (Dayton, Ohio), no. 9. doi:10.1002/stem.1436. https://www.ncbi.nlm.nih.gov/pubmed/23712774

Homing and Migration of Mesenchymal Stem Cells

Homing is another term used to describe the Migration of stem cells through your peripheral blood and across the entire endothelial vasculature system into different organs in the body.

Process of Homing and Migration | VIDEO

The ongoing issue in the subject of cell-established treatments is the delivery of the cells to the site of harm, a procedure termed “homing.” The remedial effectiveness of Mesenchymal stem cells is substantially influenced by their skill to generate juxtacrine or paracrine variables that improve regeneration from endogenous (stalk) cells. For the juxtacrine effects to be potential, migration of Mesenchymal stem cells to the diseased organs such as liver or kidney cells are recruited. Homing and migration to the tissue of harm is determined by many variables including passing rate,age of patient, amount of the delivery system, culturing growth medium, and the adult stem cells themselves among others.[1]

The regeneration centre of Thailand uses allogeneic and autologous cells in treatments that need active navigation, This procedure is better known as homing. Homing or migration of cells is the fundamental basis of modern stem cell transplantations. Likewise, the homing mechanism of cells is much needed for seeding the progenitor cells during the development stage.[2]

Homing has a direct physiological effect in homeostasis for adults. Such a state can also be amplified during stress causing recruiting of leukocytes during stem cell mobilization. Homing and cell migration is considered to be an unified, measure procedure, which is indicated by:

  • SDF1 or stromal-derived variable 1
  • SPGF – Cell Specific Growth Factors
  • SCF or stem cell growth factors
  • Activation of lymphocyte function-related antigen 1 (LFA1)
  • VLA antigen 4/5
  • CD44
  • Cytoskeleton rearrangement
  • MT1
  • MMP or Matrix Metalloproteinase activation
  • Steady secretion of MMP 2/9

Adhesion of the progenitor to endothelial cell in sinusoids under blood flow is followed by trans-endothelial migration across the physical endothelium and ECM or extracellular matrix.The injected Stem cells complete their homing journey by anchoring their specialized markets in the endosteum area and periarterial areas.[3]

Hematopoietic stem cells reside in our bone marrow but can be forced out into the bloodstream to find their way to cells in distress. This automatic reaction is what is known as mobilization and is used clinically in our therapies to help harvest large numbers of adult cells for transplantation.

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Published Clinical Citations

  • [1] ^ S.L. Seneviratne, A.P. Black, L. Jones, A.S. Bailey, G.S. Ogg, The role of skin-homing T cells in extrinsic atopic dermatitis, QJM: An International Journal of Medicine, Volume 100, Issue 1, January 2007, Pages 19–27, https://doi.org/10.1093/qjmed/hcl132

  • [2] ^ Chavakis E, Urbich C, Dimmeler S. Homing and engraftment of progenitor cells: a prerequisite for cell therapy. J Mol Cell Cardiol. 2008;45(4):514–22. https://doi.org/10.1016/j.yjmcc.2008.01.004.e

  • [3] ^ Shiba Y, Takahashi M, Hata T, Murayama H, Morimoto H, Ise H, Nagasawa T, Ikeda U. Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis. Cardiovasc Res. 2009;81(1):169–77. https://doi.org/10.1093/cvr/cvn247

Cancer Stem Cells

Cancer stem cells (CSCs) pertain to cancer cells usually found in hematologic cancers or tumors having the specific characteristics of regular stem cells. They normally have the specific capability of self-renewal and can transform into other types of cells like neural cells,skin cells,tissue cells and many other types of adult stem cells.[1]

Stem Cells and Cancer – VIDEO

Cancer stem cells used in cancer treatments are especially unique topic as they are believed to be the underlying cause of tumor metastasis and tumor recurrence. Cancer drugs can be successful in destroying a large amount of tumor cells, but often fail to induce consistent results thanks to the cells natural abilities for developing resistance to lung cancer treatments over time.[2] Cancer stem cells CSCs are always finding ways to become resistant to known pharmaceutical based cancer therapies including chemotherapy,radiation therapy and cancer drugs.[3]

To learn more about cancer treatment options at the Regeneration Center of Thailand please contact us today.

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Published Clinical Citations

Primordial Human Embryonic Germ Cells

Embryonic germ cells are pluripotent cells that originated from the early germ cells that are responsible for the formation of sperm and egg cells.[1]

Rethinking Germ Cells | Video

Embryonic germ cells are believed to mimic the properties of embryonic stem cells.

Germ cells are essentially very specialized cells that are crucial in reproduction and in regenerative medicine. Cells such as sperm,eggs and gametes eventually form a zygote that develops into a human fetus. Other cells that are involved in human reproduction are also referred to as germ cells and include gonocytes that help regulate production of sperm and eggs.[2]

All germ cells in the body carry the germline. The Germline and daughter cells are the genetic material that organisms pass to their offspring. For humans, these cells are known as haploids.[3]When two distinct sets of germ cells combine, their haploids combine to form diploid cells that can continue to replicate through cell division and eventually form into a baby.

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Published Clinical Citations

  • [1] ^ Matsumura H, Tada M, Otsuji T, Yasuchika K, Nakatsuji N, Surani A, Tada T. Targeted chromosome elimination from ES-somatic hybrid cells. Nature Methods. 2007;4:23–25.

  • [2] ^ Wilmut I, Beaujean N, de Sousa PA, Dinnyes A, King TJ, Paterson LA, Wells DN, Young LE. Somatic cell nuclear transfer. Nature. 2002;419:583–586

  • [3] ^ Molyneaux KA, Zinszner H, Kunwar PS, Scaible K, Stebler J, Sunshine MJ, O’Brien W, Raz E, Littman D, Wylie C, Lehmann R. The chamokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development. 2003;13:4279–4286.

Haploid Cell Function and Cellular Formation in Humans

UPDATED July 06, 2020 The human body contains two primary types of cells:

  1. Haploid cells
  2. Diploid cells

Haploid Vs Diploid – VIDEO

Haploid cells pertains to the number of chromosomes found in a gamete or represents half of the normal chromosome count in a particular somatic cells. The primary difference between haploid and diploid cells are the total number of chromosomes they consist of.[1]

The haploids are also called gametes. During the process of meiosis, the homologous chromosomal pairs separate to produce 2 haploid daughter cells.[2]

When sex cells such as egg and sperm meet, the combined genetic material creates a full 46 chromosomes becoming diploid.Thus human Sexual reproduction is designed as a natural method of producing genetically diverse offspring.[3]

To learn more or if you have any other questions please contact us today.

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Published Clinical Citations

  • [1] ^ Mahasup, Namfon, Paskorn Sritipsukho, Raweewan Lekskulchai, and Tippawan Hansakunachai. 2012. Effects of mirror neurons stimulation on motor skill rehabilitation in children with cerebral palsy: a clinical trial. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. https://www.ncbi.nlm.nih.gov/pubmed/23964461

  • [2] ^ Easley, Charles A, Bart T Phillips, Megan M McGuire, Jennifer M Barringer, Hanna Valli, Brian P Hermann, Calvin R Simerly, et al. 2012. Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells. Cell reports, no. 3 (August 23). doi:10.1016/j.celrep.2012.07.015. https://www.ncbi.nlm.nih.gov/pubmed/22921399

  • [3] ^ Matangkasombut, Oranart, Roongtiwa Wattanawaraporn, Keiko Tsuruda, Masaru Ohara, Motoyuki Sugai, and Skorn Mongkolsuk. 2009. Cytolethal distending toxin from Aggregatibacter actinomycetemcomitans induces DNA damage, S/G2 cell cycle arrest, and caspase- independent death in a Saccharomyces cerevisiae model. Infection and immunity, no. 2 (December 7). doi:10.1128/IAI.00857-09. https://www.ncbi.nlm.nih.gov/pubmed/19995894

Neuron Synaptic Connections & The Function of Neurotransmitters

What are Neurotransmitters?

UPDATED July 15, 2020 Neurotransmitters are the human body’s chemical messengers. These sensory neuron molecules are used by our central and peripheral nervous system to rapidly send messages between muscles and the brain or from neurons to muscles in the body.

The neuro and Gastrointestinal neurotransmitter communication starts in the synaptic cleft of 2 neuron cells. The neural synaptic gap exists between the synapses of neuron cells. All electrical signals generated by neuron cells travel along the axon and then help convert the electrical signals into chemical signals that help regulate the release of neurotransmitters resulting in a movement or desired response.

What Are Neurons?

Neurons are specialized nerve cells like neural cells & somatic motor neurons that are responsible for relaying information via neurotransmitter release. A human brain consists of well over 100 billion neurons. A neuron is the basic building foundation of cognitive function and the human nervous system.[1]

Anatomy of a Neuron – VIDEO

Messages for other cells or between neurons are sent across synapses in the brain. The anatomy of neurons is normally composed of a cell body called the axon and appendages known as dendrites. A dendrite could either be single or in multiple numbers. Traumatic Brain injuries or diseases like Alzheimer’s, ALS and Ataxia are caused when the connections between the neurons are damaged. [2]

Our current research suggests that neural derived stem cells can generate most of the various types of neurons found in the brain and the nervous system. This application is critical in regenerative medical therapies offered at the Regeneration Center[3]

What is the speed of neural signaling?

So how do we measure brain activity in people? Recent research indicates that the speed of the signals are variable and can range from milliseconds to a few seconds for neural cells to restore and reuse these powerful chemicals resulting in a nearly endless source of rapid communication. A recent speed test of neurotransmitters demonstrated that a healthy myelinated axon creates an action equivalent to the speed of roughly 120 m/s.

What is the function of neurotransmitters and how do they affect neurons?

A neurotransmitter helps to influence neurons in one of 3 ways:

  • Inhibitory
  • Excitatory
  • Modulatory

As the name sounds, inhibitory transmitters prevents the creation of electrical signals while excitatory transmitters help cause the generation of action potentials ( electrical signal ) in the receiving neurons. The ability to attach to other receptors is determined by which pose the neurotransmitter are in.

Neuromodulating neurotransmitters are slightly different in how they function as they are not limited to remaining in synaptic gaps between two ( A + B) neurons and instead can affect very large quantities of neurons in the body to act at once. Neuromodulators help to regulate large populations of neurons and operate much slower than inhibitory & excitatory neurotransmitters.

In the central nervous system, signaling and interconnections are very complex as electric impulses from one neuron to another may come from:

  • Axon to dendrite
  • Dendrite to dendrite
  • Axon to cell body
  • Cell body to cell body

Types of Neurotransmitters

There are hundreds of types of neural progenitor cells and neurotransmitters but most are generally categorized as:

  • Amino acids & indispensable amino acid – There are over 170 types of Amino acids with 20 types being considered as indispensable to the human body
  • Neuropeptides – There are over 100 known types of neuropeptides
  • Small amino molecules there are over 15 known small-molecule neurotransmitters , and neuroscientists are still discovering more about these chemical messengers

Important Neurotransmitters

One of the first and most important neurotransmitters found is a molecule named acetylcholine. Acetylcholine is a small molecule but plays a big role in managing the peripheral nervous system (PNS), where it gets used and released by neurons & motor neurons that make up the autonomic nervous system. Acetylcholine also plays an critical role in maintaining cognitive functions in the CNS. Any damage or disease of neurons in the CNS is associated with traumatic brain injuries and neurodegenerative conditions like Motor Neuron Disease,peripheral neuropathy Multiple Sclerosis and Alzheimer’s disease. New research is also being done to use Gene Therapy for treating Neurotransmitter Deficiency.

Can excitatory neurochemicals affect mood & motivation?

The main excitatory transmitter in the CNS is Glutamate and dopamine.Its a known fact that large amounts of the transmitter glutamate are released during a brain stroke. The main inhibitory neurotransmitters are derivative γ-aminobutyric acid (GABA) but other inhibitory neurotransmitters known as glycine are found in the spinal cord and usually damaged during spinal cord injuries. Low levels of dopamine in the body are linked to Parkinson’s disease while high levels of dopamine can result in schizophrenia.

Some Neurotransmitters that are found in the sympathetic nervous system are norepinephrine or Noradrenaline. These transmitters are responsible for the continued activity of organs in the human body to better control things like heart rate, blood pressure and liver function. The sympathetic nervous system is responsible for our “fight or flight responses”

Histamine is another type of monoamines and plays a very important role in neurogenesis and helping to regulate our body metabolism, temperature, helping to regulating interactions between hormones, and controlling our sleep-wake cycle which boots circulating stem cells.

Are there neurotransmitters in the gut?

Neurons that use the (monoamine) serotonin (another) helps to regulate several parts of the nervous system. Serotonin is crucial in functions such as memory, sleep, mood and appetite. These Neurotransmitters are also produced in our gastrointestinal tract. As medical science has recently learned, that peripheral produced serotonin (or dysfunction in producing these types of transmitters) has been linked to several diseases such as crohn’s, irritable bowel syndrome, cardiovascular heart disease, osteoporosis and osteoarthritis.

With each new clinical trial and passing year biologists and neuroscientists are discovering more and more about cell signaling and important chemical messengers that are critical in the proper function of the gut-brain axis that regulates overall bodily function.

To learn more about functional healthcare,stem cell treatments,the missing link, neurons and function of neurotransmitters please contact us today.

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Published Clinical Citations

  • [1] ^ Mahasup, Namfon, Paskorn Sritipsukho, Raweewan Lekskulchai, and Tippawan Hansakunachai. 2012. Effects of mirror neurons stimulation on motor skill rehabilitation in children with cerebral palsy: a clinical trial. Journal of the Medical Association of Thailand = Chotmaihet thangphaethttps://www.ncbi.nlm.nih.gov/pubmed/23964461

  • [2] ^ Tornero, Daniel, Somsak Wattananit, Marita Grønning Madsen, Philipp Koch, James Wood, Jemal Tatarishvili, Yutaka Mine, et al. 2013. Human induced pluripotent stem cell-derived cortical neurons integrate in stroke-injured cortex and improve functional recovery. Brain : a journal of neurology, no. Pt 12 (October 21). doi:10.1093/brain/awt278. https://www.ncbi.nlm.nih.gov/pubmed/24148272

  • [3] ^ Yan, Yiping, Soojung Shin, Balendu Shekhar Jha, Qiuyue Liu, Jianting Sheng, Fuhai Li, Ming Zhan, et al. 2013. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells. Stem cells translational medicine, no. 11 (October 10). doi:10.5966/sctm.2013-0080. https://www.ncbi.nlm.nih.gov/pubmed/24113065

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