Undifferentiated cells refers to a cell that has yet to develop into a particular cell variant. Undifferentiated stem cells are the very basic cells in biology that all other cells derive from. The very first few cells in an embryo are considered undifferentiated.[1]

Stem cells are basically undifferentiated cells that have the unique ability to produce many different types of cell lines. By the very definition large undifferentiated carcinoma cells lack either glandular or squamous differentiation.[2]

The term is the opposite of differentiated cells and is usually used to help describe tissue or cells that have not used paracrine cell signalling to become specialized into a particular function or structures as adult stem cells. Undifferentiated cancer cells are dangerous and often grow and spread quickly.[3]

Published Clinical Citations

• [1] ^ Hu, Kexiang, Feihu Zhao, and Qingkang Wang. 2013. Mechanical characterization of living and dead undifferentiated human adipose-derived stem cells by using atomic force microscopy. Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine, no. 12 (September 17). doi:10.1177/0954411913503064. https://www.ncbi.nlm.nih.gov/pubmed/24044923

• [2] ^ Louthrenoo, W, S Boonyaratavej, R Sittiwangkul, and W Sukitawut. 1998. Anti Ro/SSA positive undifferentiated connective tissue disease in a mother with a newborn with complete congenital heart block: a case report. Journal of the Medical Association of Thailand = Chotmaihet thangphaet, no. 8. https://www.ncbi.nlm.nih.gov/pubmed/9737117

• [3] ^ Watthanaworawit, Wanitda, Paul Turner, Claudia Turner, Ampai Tanganuchitcharnchai, Allen L Richards, Kevin M Bourzac, Stuart D Blacksell, and François Nosten. 2013. A prospective evaluation of real-time PCR assays for the detection of Orientia tsutsugamushi and Rickettsia spp. for early diagnosis of rickettsial infections during the acute phase of undifferentiated febrile illness. The American journal of tropical medicine and hygiene, no. 2 (June 3). doi:10.4269/ajtmh.12-0600. https://www.ncbi.nlm.nih.gov/pubmed/23732256.

Hematopoietic stem cells are variants specifically found in bone marrow or blood in the umbilical cord, which is responsible for the formation of platelets, as well as RBCs (red blood cells) and WBCs (white blood cells). Hematopoietic stem cells (HSc) are also known as Blood cells. These powerful cells are in charge of continuous bodycare and immune protection of every cell type of the body. This relentless work demands that blood and skin cells, have the highest power to allow adult tissue self-renewal. [1]

Hematopoietic Cells from Bone Marrow | VIDEO

The cells that form blood and immune cells are called hematopoietic stem cells (HSCs). There is literally a generation of a billion new blood cells every day. Doctors have understood and capitalized on this particular fact for over 55 years now in treating many types of medical illnesses and disorders.[2]

A hematopoietic stem cell isolated in the blood or bone marrow and can self-renew. Adults stem cells like Blood cells can identify and differentiate into many types of specialized cells. These cells can literally order your bone marrow into producing and circulating blood cells.

Cell Markers with a flow cytometer May Be Used to Recognize Hematopoietic Stem Cells for use in therapies.

Hematopoietic cells in the bone marrow ca do 4 things:
1) Renew Themselves
2) Differentiate
3) Mobilize bone marrow into circulation more cells for repairs using cytokines
4) Undergo a programmed cell death known as apoptosis

Sources of Hematopoietic Stem Cells

• Bone Marrow
• Peripheral Blood
• Placenta Blood
• Umbilical Cord Blood
• Adipose Tissue
• Embryonic Stem Cells
• Induced Pluripotent Stem Cells

Effectiveness of Peripheral Blood Vs Bone Marrow Derived Cells
Peripherally harvested from the white blood cells have a few advantages over bone marrow derived. Peripheral blood cells are much easier to obtain does not require painful needles and is much more straightforward procedure. Creating differentiated white and red blood cells are the work of HSCs and progenitor cells. [3]

Regeneration Center offers Clinical Uses of Hematopoietic Cell lines for:

• Familial Blood Disorders – allogeneic bone marrow transplants found in treatment of hereditary blood disorders, such Thalassemia and familial anemia
• Hematopoietic Cell Transplants after Cancer treatments and Chemotherapy
• Treatment of Autoimmune Diseases and Diabetes Mellitus
• Treatment of Congestive Heart Disease

To learn more about Hematopoietic stem cells or if you have any other questions or requests please contact us today.

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Published Clinical Citations

• [1] ^ Wongwuttisaroj, Natta, Sasijit Vejbaesya, Viroje Chongkolwatana, and Surapol Issaragrisil. 2012. Analysis of KIR genes in HLA-identical sibling hematopoietic stem cell transplantation in Thai patients with leukemia. Journal of the Medical Association of Thailand = Chotmaihet thangphaet, no. 10. https://www.ncbi.nlm.nih.gov/pubmed/23193738.

• [2] ^ Leelahavarong, Pattara, Usa Chaikledkaew, Suradej Hongeng, Vijj Kasemsup, Yoel Lubell, and Yot Teerawattananon. 2010. A cost-utility and budget impact analysis of allogeneic hematopoietic stem cell transplantation for severe thalassemic patients in Thailand. BMC health services research (July 16). doi:10.1186/1472-6963-10-209. https://www.ncbi.nlm.nih.gov/pubmed/20633303.

• [3] ^ Chotinantakul, Kamonnaree, and Wilairat Leeanansaksiri. 2012. Hematopoietic stem cell development, niches, and signaling pathways. Bone marrow research (July 30). doi:10.1155/2012/270425. https://www.ncbi.nlm.nih.gov/pubmed/22900188.

The medical term of “cytokine” is derived from a blending of two Greek words – “cyto” or cell and “kinos” which means movement.

Cytokine molecules exist in peptides, proteins and glyco-proteins (sugar attached). The cytokines cells come form a sizable family of molecules that can be classified into several different categories due to them not being part of a specific classification system.

Cytokine Chain Signaling – VIDEO

Cytokines markers range from the interferons that control the immune system’s reaction to disease and inflammation and also the biological agents known as interleukin.[1]

There’s some disagreement in the regenerative medical community whether or not molecules should be called cytokines or hormones but classic protein markers circulate in close nanomolar concentrations. Cytokinesis on the other hand circulate in picomolar concentration and might quickly differentiate in magnitude of nearly a thousand times its population as a response to an infection or inflammation.[2]

Cytokines cells have many sources with virtually all human cells having a nucleus effective at generating interleukin 1 (IL1), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF-alpha), especially the epithelial and endothelial cells along with macrophages. In contrast, classic hormones are only secreted from certain glands such as the kidney or pancreas that secretes insulin.

A cytokine’s movement patterns and activities may change into the very cell it had been secreted from. it can also work other damaged cells nearby or even “act” in a manner similar to the endocrine system to generate effects throughout the entire body, such as regulating body temperature for an example.

The most current category used to define cytokines are as “immunomodulating agents” or bio-agents that modulate the immune systems reactions. Cytokines are very important regulators of both innate and adaptive immune response system in humans.[3]

At the Regeneration Center of Thailand, Cytokines along with growth factors are used in most hematopoietic cord blood therapies for purposes such as:

• Self-renewal
• Quiescence
• Mobilization from the stem cell niche
• Differentiation
• Apoptosis

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

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Published Clinical Citations

• [1] ^ Chuenchitra, Thippawan, Pittapun Chaitaveep, Suchitra Sukwit, Sukchai Dettrairat, Sutchana Tabprasit, Surangrat Srisurapanon, Surapol Kohreanudom, et al. 2012. Cytokine profiles in HIV-1 subtype CRF01_AE infected individuals with different rates of diseases progression: a multiplex immunoassay. Journal of the Medical Association of Thailand = Chotmaihet thangphaet. https://www.ncbi.nlm.nih.gov/pubmed/22934457

• [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] ^ Zhang, Cheng C, and Harvey F Lodish. 2008. Cytokines regulating hematopoietic stem cell function. Current opinion in hematology, no. 4. doi:10.1097/MOH.0b013e3283007db5. https://www.ncbi.nlm.nih.gov/pubmed/18536567

Flow Cytometry use in Thai regenerative medicine combines high-data content abilities of microscopy with the high throughput analysis of captured images of cells and particles in multiple channels. The flow cytometry data file provides our cell biologists the specifications needed to understand cell population strength before stem cell treatments begin.

Basics of Flow Cytometry – VIDEO

Our stem cell bank in Bangkok uses laser guided Flow cytometers to analyze cell populations such as CD34+ hematopoietic stem cells that are in suspension. Flow cytometry machines measure the exact characteristics of stem cells as they flow in the cell culture while in suspension. ^[1]

For proper analysis of cells flow cytometry requires samples be in single cell form in culture growth medium but under suspension.

Some clinical applications for flow cytometry at the cell regeneration center of Thailand extend far beyond traditional counting of lymphocyte immunophenotyping. We also use Flow cytometers in cell cloning,to analyze micro particles in PRP platelet plasma and endothelial-derived adult stem cells,cord blood derived,placenta derived and embryonic stem cells. ^[2]

A modern flow cytometer consists of 3 systems: optics,fluids and the electronics.

• The optic system is made of lasers that illuminate nano-particles in the viewing stream  and allows optical filters to easily direct the light signals to the appropriate detectors.
• The Fluid system helps transport the actual particles in the visible stream to the laser beam to be detected i.e using markers.
• The last and most important piece is the electronics system that converts the light signals into binary electronic signals for computers to understand ^[3]

Modern flow cytometry allows for special laser instruments to identify and sort cells based on their markers. The same system can also be used to customize delivery by sorting out undesired cell types by sorting them out using charged particles to deflect the undesired cell phenotypes.^[4]

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Published Clinical Citations

• [1] ^ E A M Eldebaky, H M E Afifi, S A Pessar, A M S Ahmed, Implication of Flow Cytometry-Based Maturity Score in Risk Stratification of Acute Myeloid Leukemia in Adult Egyptians, QJM: An International Journal of Medicine, Volume 113, Issue Supplement_1, March 2020, hcaa044.006, https://doi.org/10.1093/qjmed/hcaa044.006

• [2] ^ S. Elias, O. Almogi-Hazan, M. Aker, A. Ben-Yehuda, A. Bayya, Y. Tal, A diagnostic challenge: PCP in a non-HIV patient, QJM: An International Journal of Medicine, Volume 104, Issue 10, October 2011, Pages 889–891, https://doi.org/10.1093/qjmed/hcq208

• [3] ^ R M Said, H M Abdelbary, A M Elaffifi, R A El-Gamal, K A Almuawi, Flow cytometric assessment of CD30 expression in adult patients with acute leukemia, QJM: An International Journal of Medicine, Volume 111, Issue suppl_1, December 2018, hcy200.092, https://doi.org/10.1093/qjmed/hcy200.092

• [4] ^ A.C. Phillips, D. Carroll, C.R. Gale, M. Drayson, G.D. Batty, Lymphocyte cell counts in middle age are positively associated with subsequent all-cause and cardiovascular mortality, QJM: An International Journal of Medicine, Volume 104, Issue 4, April 2011, Pages 319–324, https://doi.org/10.1093/qjmed/hcq199

Cloning is the process of generating replicas of a particular cell or organism, or even a portion of DNA.

What is Cloning? – Video

Cloning a stemcell means to doctors are able to produce a population of cells from just one single cell.[1] The Cloning process produces unspecialized stem cells that are induced or differentiated to grow into various types of adult stem cells. These advances made through cloning embryonic stem cells have led to revolutionary new regenerative therapies and also to prevent mitochondrial diseases from being passed from mother to child.[2] The development of cloning technology in Thailand has led to new methods of medicine delivery and is improving our understanding of human development and genetics.[3]

There is a lot of ethical debate over whether or not therapeutic cloning should be used. Cloning process is reproduced in vitro through asexually Cloning. This process refers to creating copies of DNA fragments and is also called molecular cloning ), cells (cell cloning), or organisms.

Organism cloning or “reproductive cloning” refers to the process of creating a new multicellular organism that is 100% genetically identical to each other. There are also many potential dangers in cloning human cells. Many scientists believe that human cloning is only about 10 or 15 years away still because the process is far more difficult than cloning a sheep. Human reproductive cloning is Banned in most countries and also not allowed in Thailand.[4]

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Published Clinical Citations

• [1] ^Imsoonthornruksa, Sumeth, Chanchao Lorthongpanich, Anawat Sangmalee, Kanokwan Srirattana, Chuti Laowtammathron, Wanchai Tunwattana, Wachiravit Somsa, Mariena Ketudat-Cairns, Takashi Nagai, and Rangsun Parnpai. 2011. The effects of manipulation medium, culture system and recipient cytoplast on in vitro development of intraspecies and intergeneric felid embryos. The Journal of reproduction and development, no. 3 (February 14). https://www.ncbi.nlm.nih.gov/pubmed/21325740

• [2] ^ Imsoonthornruksa, Sumeth, Kanokwan Srirattana, Wanwisa Phewsoi, Wanchai Tunwattana, Rangsun Parnpai, and Mariena Ketudat-Cairns. 2012. Segregation of donor cell mitochondrial DNA in gaur-bovine interspecies somatic cell nuclear transfer embryos, fetuses and an offspring. Mitochondrion, no. 5 (July 21). doi:10.1016/j.mito.2012.07.108. https://www.ncbi.nlm.nih.gov/pubmed/22824460

• [3] ^ Liu, J, Y Wang, J Su, Y Luo, F Quan, and Y Zhang. 2013. Nuclear donor cell lines considerably influence cloning efficiency and the incidence of large offspring syndrome in bovine somatic cell nuclear transfer. Reproduction in domestic animals = Zuchthygiene, no. 4 (January 16). doi:10.1111/rda.12140. https://www.ncbi.nlm.nih.gov/pubmed/23320388

• [4] ^ Imsoonthornruksa, Sumeth, Anawat Sangmalee, Kanokwan Srirattana, Rangsun Parnpai, and Mariena Ketudat-Cairns. 2012. Development of intergeneric and intrageneric somatic cell nuclear transfer (SCNT) cat embryos and the determination of telomere length in cloned offspring. Cellular reprogramming, no. 1 (January 4). doi:10.1089/cell.2011.0054. https://www.ncbi.nlm.nih.gov/pubmed/22217197

The process of Cell meiosis occurs through cell division. In this Stage, the cells generate gametes (egg or sperm) and carry half of the normal chromosome count. After fertilization, the resulting embryo formation (after gamete) shall then finally contain the right number of chromosomes. Meiosis is a special type of cell differentiation that produces gametes with half as many chromosomes. Meiosis I is a type of cell division unique to germ cells, while meiosis II that is very similar to mitosis.[1]

The First stage of Meiosis “I” reduces the ploidy levels from 2n to just n while the second stage of Meiosis “II” divides the last remaining set of chromosomes in a “mitosis-like” process.). The old name for meiosis was reduction/ division. Two daughter cells are formed during telophase I. These usually go immediately into the second cell division (meiosis II) to separate the chromatids.[2]

The steps involved in meiosis are similar to mitosis and even have the same names.Alleles are what help to facilitate this drive can also spread if they team up with the meiotic drive alleles. During the reduction division stage of meiosis I, cells go from a diploid to a haploid state.

What came first…the chicken or the egg?

The term “disjunction” describes the separation of the chromosomes in meiosis stage I or “sister” chromatids in meiosis stage II. NOTE** There is also an alternative theory about the origins of meiosis. This theory states that meiosis division evolved from mitosis. To better understand meiosis in eukaryotes, it’s very important to understand how meiosis can differentiate into a single cell eukaryotes. This is a vital function of the mitosis separation process. [3]

The mechanism by which meiosis occurs is the process to joining two genomes. That second division divides the number of chromosomes in half.

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Published Clinical Citations

• [1] ^ Gerton, J. L., & Hawley, R. S. Homologous chromosome interactions in meiosis: Diversity amidst conservation. Nature Reviews Genetics 6, 477–487 (2005) doi:10.1038/nrg1614

• [2] ^ Lopez-Maury, L., Marguerat, S., & Bahler, J. Tuning gene expression to changing environments: From rapid responses to evolutionary adaptation. Nature Reviews Genetics 9, 583–593 (2008) doi:10.1038/nrg2398

• [3] ^ Marston, A. L., & Amon, A. Meiosis: Cell-cycle controls shuffle and deal. Nature Reviews Molecular Cell Biology 5, 993–1008 (2004) doi:10.1038/nrm1526