14.7: Stem Cells - Biology

14.7: Stem Cells - Biology

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

Stem cells are cells that divide by mitosis to form either two stem cells, thus increasing the size of the stem cell "pool", or one daughter that goes on to differentiate, and one daughter that retains its stem-cell properties. How the choice is made is still unknown. However, several genes have been found whose activity prevents a daughter cell from differentiating.

Types of Stem Cells

Several adjectives are used to describe the developmental potential of stem cells; that is, the number of different kinds of differentiated cell that they can become.

  1. Totipotent cells. In mammals, totipotent cells have the potential to become any type in the adult body and any cell of the extraembryonic membranes (e.g., placenta). The only totipotent cells are the fertilized egg and the first 4 or so cells produced by its cleavage (as shown by the ability of mammals to produce identical twins, triplets, etc.). In mammals, the expression totipotent stem cells is a misnomer — totipotent cells cannot make more of themselves.
  2. Pluripotent stem cells. These are true stem cells, with the potential to make any differentiated cell in the body (but probably not those of the placenta which is derived from the trophoblast).

Three types of pluripotent stem cells occur naturally:

  • Embryonic Stem (ES) Cells. These can be isolated from the inner cell mass (ICM) of the blastocyst — the stage of embryonic development when implantation occurs. For humans, excess embryos produced during in vitro fertilization (IVF) procedures are used. Harvesting ES cells from human blastocysts is controversial because it destroys the embryo, which could have been implanted to produce another baby (but often was simply going to be discarded).
  • Embryonic Germ (EG) Cells. These can be isolated from the precursor to the gonads in aborted fetuses.
  • Embryonic Carcinoma (EC) Cells. These can be isolated from teratocarcinomas, a tumor that occasionally occurs in a gonad of a fetus. Unlike the other two, they are usually aneuploid.

All three of these types of pluripotent stem cells can only be isolated from embryonic or fetal tissue. They can be grown in culture, but only with special methods to prevent them from differentiating.

In mice and rats, embryonic stem cells can also:

  • contribute to the formation of a healthy chimeric adult when injected into a blastocyst which is then implanted in a surrogate mother;
  • enter the germline of these animals; that is, contribute to their pool of gametes;
  • develop into teratomas when injected into immunodeficient (SCID) mice. These tumors produce a wide variety of cell types representing all three germ layers (ectoderm, mesoderm, and endoderm).

Using genetic manipulation in the laboratory, pluripotent stem cells can now be generated from differentiated cells. These induced pluripotent stem cells (iPSCs) are described below.

  1. Multipotent stem cells. These are true stem cells but can only differentiate into a limited number of types. For example, the bone marrow contains multipotent stem cells that give rise to all the cells of the blood but not to other types of cells. Multipotent stem cells are found in adult animals; perhaps most organs in the body (e.g., brain, liver, lungs) contain them where they can replace dead or damaged cells. These adult stem cells may also be the cells that — when one accumulates sufficient mutations — produce a clone of cancer cells.

Stem Cells for Human Therapy

The Dream

Many medical problems arise from damage to differentiated cells. Examples:

  • Type 1 diabetes mellitus where the beta cells of the pancreas have been destroyed by an autoimmune attack
  • Parkinson's disease; where dopamine-secreting cells of the brain have been destroyed
  • Spinal cord injuries leading to paralysis of the skeletal muscles
  • Ischemic stroke where a blood clot in the brain has caused neurons to die from oxygen starvation
  • Multiple sclerosis with its loss of myelin sheaths around axons
  • Blindness caused by damage to the cornea

The great developmental potential of stem cells has created intense research into enlisting them to aid in replacing the lost cells of such disorders. While progress has been slow, some procedures already show promise. Using multipotent "adult" stem cells.

  • culturing human epithelial stem cells and using their differentiated progeny to replace a damaged cornea. This works best when the stem cells are from the patient (e.g. from the other eye). Corneal cells from another person (an allograft) are always at risk of rejection by the recipient's immune system.
  • the successful repair of a damaged left bronchus using a section of a donated trachea that was first cleansed of all donor cells and then seeded with the recipient's epithelial cells and cartilage-forming cells grown from stem cells in her bone marrow. So far the patient is doing well and needs no drugs to suppress her immune system.

Using differentiated cells derived from embryonic stem (ES) cells. Phase I clinical trials are underway to assess the safety of

  • injecting retinal cells derived from ES cells
    • into the eyes of young people with an inherited form of juvenile blindness;
    • into the eyes of adults with age-related macular degeneration.
  • injecting glial cells derived from ES cells into patients paralyzed by spinal cord injuries.

The Immunological Problems

One major problem that must be solved before human stem cell therapy becomes a reality is the threat of rejection of the transplanted cells by the host's immune system (if the stem cells are allografts; that is, come from a genetically-different individual).

A Possible Solution

One way to avoid the problem of rejection is to use stem cells that are genetically identical to the host. This is already possible in the rare situations when the patient has healthy stem cells in an undamaged part of the body (like the stem cells being used to replace damaged corneas). But even where no "autologous" stems cells are available, there may be a solution: using somatic-cell nuclear transfer .

In this technique,

  1. An egg has its own nucleus removed and replaced by
  2. a nucleus taken from a somatic (e.g., skin) cell of the donor.
  3. The now-diploid egg is allowed to develop in culture to the blastocyst stage when
  4. embryonic stem cells can be harvested and grown up in culture.
  5. When they have acquired the desired properties, they can be implanted in the donor with no fear of rejection.

Using this procedure it possible to not only grow blastocysts but even have these go on to develop into adult animals — cloning — with a nuclear genome identical to that of the donor of the nucleus. The first successful cloning by SCNT was with amphibians. Later, mammals such as sheep (Dolly), cows, mice and others were successfully cloned. And in the 11 November 2007 issue of Science, researchers in Oregon reported success with steps 1–4 in rhesus monkeys (primates like us).

Their procedure:

  • Remove the spindle and thus all nuclear material from secondary oocytes at metaphase of meiosis II.
  • Fuse each enucleated egg with a skin cell taken from a male monkey.
  • Culture until the blastocyst stage is reached.
  • Extract embryonic stem cells from the inner cell mass.
  • Establish that they have the nuclear genome of the male (but mostly the mitochondrial genome of the female).
  • Culture with factors to encourage differentiation: they grew cardiac muscle cells (which contracted), and even neuron-like cells.
  • Inject into SCID mice and examine the tumors that formed. These contained cells of all three germ layers: ectoderm, mesoderm, and endoderm.
  • However, even after more than 100 attempts, they have not been able to implant their monkey blastocysts in the uterus of a surrogate mother to produce a cloned monkey.

This should reassure people who view with alarm the report in May 2013 by the same workers that they have finally succeeded in producing embryonic stem cells (ESCs) using SCNT from differentiated human tissue. The workers assure us that they will not attempt to implant these blastocysts in a surrogate mother to produce a cloned human. And their failure with monkeys suggests that they would fail even if they did try.

While cloning humans still seems impossible, patient-specific ESCs

  • could be used in cell-replacement therapy or, failing that,
  • provide the material for laboratory study of the basis of — and perhaps treatment of — genetic diseases.

Whether they will be more efficient and more useful than induced pluripotent stem cells remains to be seen.

Questions that Remain to be Answered

  • Imprinted Genes. Sperm and eggs each contain certain genes that carry an "imprint" identifying them later in the fertilized egg as being derived from the father or mother respectively. Creating an egg with a nucleus taken from an adult cell may not allow a proper pattern of imprinting to be established. When the diploid adult nucleus is inserted into the enucleated egg (at least those of sheep and mice), the new nucleus becomes "reprogrammed". What reprogramming actually means still must be learned, but perhaps it involves the proper methylation and demethylation of imprinted genes. For example, the inactive X chromosome in adult female cells must be reactivated in the egg, and this actually seems to happen.
  • Aneuploidy. In primates (in contrast to sheep, cattle, and mice), the process of removing the resident nucleus causes molecules associated with the centrosome to be lost as well. Although injecting a donor nucleus allows mitosis to begin, spindle formation may be disrupted, and the resulting cells fail to get the correct complement of chromosomes (aneuploidy).
  • Somatic Mutations. This procedure also raises the spectre of amplifying the effect(s) of somatic mutations. In other words, mutations that might be well-tolerated in a single somatic cell of the adult (used to provide the nucleus) might well turn out to be quite harmful when they become replicated in a clone of cells injected later into the patient.
  • Political Controversy. The goal of this procedure (which is often called therapeutic cloning even though no new individual is produced) is to culture a blastocyst that can serve as a source of ES cells. But that same blastocyst could theoretically be implanted in a human uterus and develop into a baby that was genetically identical to the donor of the nucleus. In this way, a human would be cloned. And in fact, Dolly and other animals are now routinely cloned this way. The spectre of this is so abhorrent to many that they would like to see the procedure banned despite its promise for helping humans. In fact, many are so strongly opposed to using human blastocysts — even when produced by nuclear transfer — that they would like to limit stem cell research to adult stem cells (even though these are only multipotent).

Possible Solutions to the Ethical Controversy

Induced pluripotent stem cells (iPSCs)

A promising alternative to the use of embryonic stem cells in human therapy are recently-developed methods of genetically reprogramming the nuclei of differentiated adult cells so that they regain the pluripotency of embryonic stem (ES) cells.

In June 2007, three laboratories reported that introducing extra copies of only 4 genes into adult mouse skin cells (fibroblasts) enables them to regain the properties of ES cells. When these cells, named induced pluripotent stem cells (iPSCs for short), were placed in mouse blastocysts, they participated in building all the tissues of the chimeric mice that resulted. (When placed in tetraploid (4n) blastocysts — unable by themselves to develop normally — embryos were formed that thus were clones of the skin cell donor.) The four genes: c-Myc, Sox2, Oct3/4, Klf4.

By 2009, several labs had succeeded in producing fertile adult mice from iPSCs derived from mouse embryonic fibroblasts. This shows that iPSCs are just a capable of driving complete development (pluripotency) as embryonic stem cells.

Reprogramming works in humans, too! Using the same four genes, the Yamanaka lab in Japan reported on 20 November 2007, that they now had reprogrammed human skin cells to become induced pluripotent stem cells (iPSCs). And the Thomson lab in Wisconsin accomplished the same thing using SOX2, OCT4, NANOG, and LIN28.

Further evidence of the remarkable role played by these few genes is the finding that during normal embryonic development of the zebrafish, the same or similar genes (SoxB1, Oct4, Nanog) are responsible for turning on the genes of the zygote. Earlier in development of the blastula, all the genes being expressed (including these) are the mother's — mRNAs and proteins that the mother deposited in the unfertilized egg. It makes sense that the same proteins that can reprogram a differentiated cell into a pluripotent state (iPSCs) are those that produce the pluripotent cells of the early embryo.

These achievements open the possibility of

  • creating cells for laboratory study of the basis of genetic diseases.
    Examples: researchers have succeeded in deriving iPSCs from
    • patients with amyotrophic lateral sclerosis (ALS, "Lou Gehrig's disease"), and then causing them to differentiate into motor neurons (the cells affected in the disease) for study of their properties;
    • the skin cells of a patient with an inherited heart disease (long QT syndrome) and causing these to differentiate into beating heart cells for study in the laboratory.
    • The Jaenisch lab reported in the 6 March 2009 issue of Cell that they have succeeded in making iPSCs (they call them hiPSCs) from fibroblasts taken from patients with Parkinson's disease. The cells were then differentiated into dopamine-releasing cells — the cells lacking in this disease. What is particularly exciting is that they accomplished this after using the Cre-lox system to remove all the genes (e.g., SOX2, OCT4, KLF4) needed for reprogramming the fibroblasts to an embryonic-stem-cell-like condition.
    • Since that report, other laboratories — using other methods — have also created iPSCs from which all foreign DNA (vector and transgenes) has been removed. Not only should such cells be safer to use in therapy, but these results show that the stimulus to reprogram a differentiated cell into a pluripotent state need only be transitory.
  • creating patient-specific cell transplants — avoiding the threat of immunological rejection — that could be used for human therapy.

    Therapy with iPSCs has already been demonstrated in mice. Three examples:

    1. The Jaenisch lab in Cambridge, MA reported (in Science, 21 December 2007) that they had successfully treated knock-in mice that make sickle-cell hemoglobin with the human βS genes (and show many of the signs of sickle-cell disease in humans) by
    • harvesting some fully-differentiated fibroblasts from a sickle-cell mouse;
    • reprogramming these to become iPSCs by infecting them with Oct4, Sox2, Klf4, and c-Myc;
    • then removing (using the Cre-lox system) the c-Myc to avoid the danger of this oncogene later causing cancer in the recipient mice;
    • replacing the βS genes in the iPSCs with normal human βA genes;
    • coaxing, with a cocktail of cytokines, these iPSCs to differentiate in vitro into hematopoietic (blood cell) precursors;
    • injecting these into sickle-cell mice that had been irradiated to destroy their own bone marrow (as is done with human bone marrow transplants). (Although the recipient mice were different animals from the fibroblast donor, they were of the same inbred strain and thus genetically the same — like identical human twins. So the procedure fully qualifies as "patient-specific", i.e., with no danger of the injected cells being rejected by the recipient's immune system.)

    The result: all the signs of sickle-cell disease (e.g., anemia) in the treated animals showed marked improvement.

    2. In the 25 July 2013 issue of Nature, a team of Japanese scientists report that they were able to manufacture three-dimensional buds of human liver cells. Their process:
    • create human iPSCs from human fibroblasts using the techniques described above;
    • treat these with the substances needed for them to differentiate in liver cell precursors;
    • culture these with a mixture of human endothelial cells and mesenchymal stem cells (to mimic the conditions that occur in normal embryonic development of the liver);
    • implant the resulting solid masses (buds) of liver-like cells into immunodeficient mice.

    The result: the implanted buds developed a blood supply and the mice began to secrete human albumin, human alpha-1-antitrypsin, and to to detoxify injected chemicals just as human livers do.

    3. Workers in the Melton lab at Harvard University reported in the 9 October 2014 issue of Cell that they had succeeded in differentiating large numbers of human beta cells from human iPSCs (as well as from human ES cells). When transplanted into diabetic mice, these cells brought their elevated blood sugar levels back down.

Let us hope that what works in mice can someday be developed into a safe therapy that will work in humans. (In the case of Type 1 diabetes mellitus, however, even patient-derived beta cells will still be at risk of the same autoimmune rejection that caused the disease in the first place.)

Despite these successes, iPSCs may not be able to completely replace the need for embryonic stem cells and may even be dangerous to use in human therapy. Several groups have found that human iPSCs contain mutations as well as epigenetic patterns (e.g., methylation of their DNA) that are not found in embryonic stem cells. Some of the mutations are also commonly found in cancer cells.

Other approaches being explored

  • ES cells can be derived from a single cell removed from an 8-cell morula. The success of preimplantation genetic diagnosis (PGD) in humans shows that removing a single cell from the morula does not destroy it — the remaining cells can develop into a blastocyst, implant, and develop into a healthy baby. Furthermore, the single cell removed for PGD can first be allowed to divide with one daughter used for PGD and the other a potential source of an ES cell line.
  • In altered nuclear transfer (ANT) — a modified version of SCNT (somatic-cell nuclear transfer) — a gene necessary for later implantation (Cdx2 — encoding a homeobox transcription factor) is turned off (by RNA interference) in the donor nucleus before the nucleus is inserted into the egg. The blastocyst that develops
    • has a defective trophoblast that cannot implant in a uterus
    • but the cells of the inner cell mass are still capable of developing into cultures of ES cells. (The gene encoding the interfering RNA can then be removed using the Cre/loxP technique.)
  • Jose Cibelli and his team at Advanced Cell Technology reported in the 1 February 2002 issue of Science that they had succeeded inIf this form of cloning by parthenogenesis works in humans [It does! — success with unfertilized human eggs was reported in June 2007.], it would have
    • stimulating monkey oocytes to begin dividing without completing meiosis II (therefore still 2n)
    • growing these until the blastocyst stage, from which they were able to harvest
    • ES cells.
    • the advantage that no babies could be produced if the blastocyst should be implanted (two identical genomes cannot produce a viable mammal — probably because of incorrect imprinting);
    • the disadvantage that it will only help females (because only they can provide an oocyte!) (But men may have a procedure that works for them next.)
  • On 24 March 2006, Nature published an online report that a group of German scientists had been able to derive pluripotent stem cells from the stem cells that make spermatogonia in the mouse. Both in vitro and when injected into mouse blastocysts, these cells differentiated in a variety of ways including representatives of all three germ layers. If this could work in humans, it would
    • provide a source of stem cells whose descendants would be "patient-specific"; that is, could be transplanted back into the donor (men only!) without fear of immune rejection.
    • avoid the controversy surrounding the need to destroy human blastocysts to provide embryonic stem cells.
  • The 7 January 2007 issue of Nature Biotechnology reports the successful production of amniotic fluid-derived stem cells ("AFS"). These are present in the amniotic fluid removed during amniocentesis. With the proper culture conditions, they have been shown to be able to differentiate into a variety of cell types includingSo these cells are pluripotent. Although perhaps not as versatile as embryonic stem cells, they are more versatile than adult stem cells.
    • ectoderm (neural tissue)
    • mesoderm (e.g., bone, muscle)
    • endoderm (e.g., liver)

Applied to humans, none of the above procedures would involve the destruction of a potential human life.

14.7: Stem Cells - Biology

All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited.

Feature Papers represent the most advanced research with significant potential for high impact in the field. Feature Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review prior to publication.

The Feature Paper can be either an original research article, a substantial novel research study that often involves several techniques or approaches, or a comprehensive review paper with concise and precise updates on the latest progress in the field that systematically reviews the most exciting advances in scientific literature. This type of paper provides an outlook on future directions of research or possible applications.

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

14.7: Stem Cells - Biology

All articles published by MDPI are made immediately available worldwide under an open access license. No special permission is required to reuse all or part of the article published by MDPI, including figures and tables. For articles published under an open access Creative Common CC BY license, any part of the article may be reused without permission provided that the original article is clearly cited.

Feature Papers represent the most advanced research with significant potential for high impact in the field. Feature Papers are submitted upon individual invitation or recommendation by the scientific editors and undergo peer review prior to publication.

The Feature Paper can be either an original research article, a substantial novel research study that often involves several techniques or approaches, or a comprehensive review paper with concise and precise updates on the latest progress in the field that systematically reviews the most exciting advances in scientific literature. This type of paper provides an outlook on future directions of research or possible applications.

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Research using sex as a variable has revealed sex differences in the properties of some adult stem cells. Findings include:

  • 1. Differences in Mesenchymal Stem Cell (MSC) Activation
    Mesenchymal stem cells, which can be derived from bone marrow and other tissues, can differentiate into bone, fat, muscle, connective tissue, and cartilage (Oreffo et al., 2005). Crisostomo and colleagues demonstrated that sex differences exist in the activation of mesenchymal stem cells (MSC). Researchers stressed murine MSCs in vitro with hypoxia, lipopolysaccharide (LPS), and hydrogen peroxide: they demonstrated that “activation” differed by cell sex: XX cells produced more vascular endothelial growth factor (VEGF, which promotes cell proliferation) and less tumor necrosis factor alpha (TNF-α, which promotes inflammation and apoptosis) than XY cells (Crisostomo et al., 2007).
  • 2. Differences in Muscle-Derived Stem Cell (MDSC) Regenerative Capacity
    MDSCs have the capacity for myocardial repair as well as skeletal muscle repair. They may also be useful for treating muscular dystrophy, for which existing treatments have limited effect (Jankowski et al., 2002).
  • MDSC cell lines display variability in regenerative ability. Using mdx mice, which spontaneously develop muscular dystrophy, Deasy et al. demonstrated that cell sex, independent of other variables such as immune response and exogenous estrogenic effects, exerts a strong effect on regenerative capacity. The mechanism behind these differences is an active area of research.
  • Deasy et al. found significant sex differences in regeneration capacity in vivo, with XX cells yielding a higher regeneration index (RI) than XY cells. In vivo studies took advantage of the fact that mdx mouse muscle fibers lack the protein dystrophin researchers determined RI by quantifying muscle fibers generated from stem cells (i.e., those with dystrophin). Even though all MDSCs could differentiate into dystrophin-expressing fibers in vitro, only XX MDSCs could regenerate robustly in vivo (Deasy et al., 2007).

These sex differences may be therapeutically relevant—but because many variables besides sex influence cell behavior, and because the traits of an “ideal” cell type differ depending on the therapy in question, such differences do not indicate that cells of a given sex are broadly therapeutically superior to cells of the other sex. In clinical research using stem cells, there is a “lack [of] direct comparisons of different cell types in clearly defined, clinically relevant models of disease” (Zenovich et al., 2007).

About the Editor

Anthony Atala

Anthony Atala, M.D., is the Director of the Wake Forest Institute for Regenerative Medicine, and the W.H. Boyce Professor and Chair of the Department of Urology at Wake Forest University. Dr. Atala is a practicing surgeon and a researcher in the area of regenerative medicine. His current work focuses on growing new human cells, tissues and organs.

Dr. Atala works with several journals and serves in various roles, including Editor-in-Chief of Current Stem Cell Research and Therapy, and Therapeutic Advances in Urology as Associate Editor of the Journal of Tissue Engineering and Regenerative Medicine, The Journal of Rejuvenation Research, Nanotechnology in Engineering and Medicine, Gene Therapy and Regulation, and Current Reviews in Urology as Executive Board Member or Section Editor of the journal Tissue Engineering and International Journal of Artificial Organs, and as Editorial Board member of the International Journal of Stem Cells, Stem Cell Review Letters, Expert Opinion on Biological Therapy, Biomedical Materials, Recent Patents on Regenerative Medicine, the Journal of the American College of Surgeons, the Journal of Urology, BMC Urology, Urology, and Current Opinion in Urology.

Dr. Atala is a recipient of the US Congress funded Christopher Columbus Foundation Award, bestowed on a living American who is currently working on a discovery that will significantly affect society, and the Gold Cystoscope Award for advances in his field. Dr. Atala was named by Scientific American as a Medical Treatments Leader of the Year for his contributions to the fields of cell, tissue and organ regeneration. In 2006, he was named by Fast Company magazine as one of 50 people who “will change how we work and live over the next 10 years. Dr. Atala’s work was listed as Discover Magazine`s Number 1 Top Science Story of the Year in the field of medicine, and as Time Magazine’s top 10 medical breakthroughs of the year in 2007. A Time Magazine poll ranked Dr. Atala as the 56th most influential person of the year in 2007. Esquire Magazine in 2008 named Dr. Atala one of the 75 most influential persons of the 21st century. Fast Company Magazine named Dr. Atala one of 100 Most Creative People in Business in 2009. Dr. Atala was featured in U.S. News & World Report as one of “14 Medical Pioneers Who Aren’t Holding Back.”

Dr. Atala has led or served several national professional and government committees, including the National Institutes of Health working group on Cells and Developmental Biology, and the National Institutes of Health Bioengineering Consortium. He is currently an NIH “Quantum Grant” awardee. Dr. Atala heads a team of over 250 physicians and researchers. Ten applications of technologies developed in Dr. Atala's laboratory have been used clinically. He is the editor of nine books, including Minimally Invasive Urology, Methods of Tissue Engineering, Principles of Regenerative Medicine, and Foundations of Regenerative Medicine, and has published more than 300 journal articles and has applied for or received over 200 national and international patents.

Affiliations and Expertise

Director, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

Key Features

  • Diligently covers all the aspects related to stem cell biology and tissue engineering in dental sciences: basic science, research, clinical application and commercialization
  • Provides detailed descriptions of new, modern technologies, fabrication techniques employed in the fields of stem cells, biomaterials and tissue engineering research including details of latest advances in nanotechnology
  • Includes a description of stem cell biology with details focused on oral and craniofacial stem cells and their potential research application throughout medicine
  • Print book is available and black and white, and the ebook is in full color

Healing is a comprehensive process. Your entire body responds to an injury, even if it is localized. For instance, when you twist your ankle, your nearby muscles compensate. You may experience a rush of adrenaline to compensate for the pain. Your circulation even reacts to the trauma by increasing its pulse.

This last point is a key matter of research and innovation. There are healing properties in human plasma that can provide elevated results when properly applied. The platelets in your blood are designed to clot and cradle wounds, but they also communicate with one another chemically. Platelets form a cohesive system that embraces healing and amplifies wellness.

By isolating your platelets, Dr. Haasis can create a serum called PRP (platelet-rich plasma) from your own blood. This compound is able to respond to damaged tissue by targeting it precisely and speeding up the healing process. PRP therapy can be conducted in conjunction with other disciplines, like stem cell therapy.

Dr. Haasis is also a master of exosome therapy. This is another procedure that utilizes the body’s internal messaging system. Exosomes are the secretions from cells that facilitate growth and healing. By navigating the fascinating possibilities of exosome research, Dr. Haasis is able to control the conversation between your cells. Injuries now have a voice, and exosomes are doing the talking.

You deserve the best care at the right price. The cost of your stem cell therapy depends on several factors: the viability of your own cells, the extent of the damage being treated, and the number of sessions required to achieve a successful outcome. Dr. Haasis will provide transparent pricing at every step in the process, so please contact our clinic and start a conversation about your best self.

Direct Reprogramming of Mouse Fibroblasts into Functional Skeletal Muscle Progenitors

Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to dystrophin-expressing myofibers upon transplantation in vivo. Notably, a subset of transplanted iMPCs maintain Pax7 expression and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7 + cells and require Pax7 itself for maintenance. Finally, we show that myogenic progenitor cell lines can be established from muscle tissue following small-molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple cell types.

Keywords: MyoD Pax7 direct lineage reprogramming induced muscle progenitor cells muscular dystrophy satellite cells skeletal muscle small molecules transplantation.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

L.N.T.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript H.-P.N., M.N.D., A.B.V., P.T.M.D.: conception and design, collection and/or assembly of data, data analysis, manuscript writing, final approval of manuscript H.B.T.P., D.N.V., K.T.T., T.D.T.T., B.D.D., A.N.T.P., N.F., M.H.: collection and/or assembly of data, data analysis and interpretation, manuscript writing, final approval of manuscript.

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Watch the video: In vitro chondrogenic differentiation of mesenchymal stem cells in alginate scaffolds (August 2022).