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Thread: Cell Therapy - Embryonic or Fetal sheep cells

  1. #1

    Cell Therapy - Embryonic or Fetal sheep cells

    There was a doctor called Prof. Niehans many many years ago who worked with sheep embryonic or fetal cells and injected them in various disorders.
    He did have a lot of success and his therapy is still used in countries like Germany, switzerland, in some parts of the US.
    Can somebody explain the difference of human and animal embryonic cells? Which of them works better in the human body?
    It is said that the cells from embryonic sheep cells find their way to the affected/diseased organ/tissue, e.g if you take heart cells from the sheep and inject them to you, then they will find their way to your heart.
    Does anybody of you know if HUMAN embryonic cells do the same I mean finding their way to the affected/diseased tissue/organ??
    This finding was confirmed by a study. Embryonic sheep cells are also not disgusted by the human immune-system.
    Since I suffer from a muscular dystrophy I will probably take this treatment, but I would like to hear your opinions about such therapy.

  2. #2
    Quote Originally Posted by Fight_for_the_Cure_2007
    There was a doctor called Prof. Niehans many many years ago who worked with sheep embryonic or fetal cells and injected them in various disorders.
    He did have a lot of success and his therapy is still used in countries like Germany, switzerland, in some parts of the US.
    Can somebody explain the difference of human and animal embryonic cells? Which of them works better in the human body?
    It is said that the cells from embryonic sheep cells find their way to the affected/diseased organ/tissue, e.g if you take heart cells from the sheep and inject them to you, then they will find their way to your heart.
    Does anybody of you know if HUMAN embryonic cells do the same I mean finding their way to the affected/diseased tissue/organ??
    This finding was confirmed by a study. Embryonic sheep cells are also not disgusted by the human immune-system.
    Since I suffer from a muscular dystrophy I will probably take this treatment, but I would like to hear your opinions about such therapy.
    Fight,

    Niehans is a Swiss doctor who developed a method of making cell extracts and using these extracts to rejuvenate and revitalize the body (Source). Although he is called the father of cellular therapy, the therapy that he developed is not cellular therapy at all but rather treatment of extracts of cells (Source). In early half of the 20th Century, we did not have or know most of the proteins in cells. Therefore, the only way to get these proteins and factors was to extract them from living cells. Niehans developed a means of lyophilizing the cells and obtaining these factors without breaking down the protein. These extracts are then injected into people who may be lacking in certain factors. For example, in those days, it was the only way to obtain parathyroid hormone to treat people with parathyroid hormone deficiency.

    There has been a great deal of interest in use of animal stem cells, as opposed to human stem cells. In general, animal cell transplants (called xenografts) are rapidly rejected by the immune system. The cells are not only rejected by the standard immune mechanism mediated by antibodies, complement fixation, and attraction of macrophages to come and eat them. Animal cells may also attract a group of cells called natural killer cells (NK cells) that automatically recognize foreign cells from another species. NK cells automatically recognize bacteria and viruses, as well as cancer cells, without the need for an antibody response to develop.

    Embryonic stem cells tend to be less immunogenic (i.e. does not stimulate as much immune response) as adult cells. However, this is not true of the progeny of the embryonic stem cells. In other words, even though the embyronic stem cells may not be rejected, the cells that they produce will express antigens that will stimulate the immune system to reject them. There is now a growing theory that embryonic stem cells (whether from human or animals) are anti-immune and somehow turn off the immune cells.

    Note that a similar anti-immune claim has been made for mesenchymal stem cells isolated from bone marrow cells. Because these cells have such potent anti-immune effects, they may prevent immune attack on other cells. Several clinical trial are now testing the effects of mesenchymal stem cells to prevent an autoimmune condition called graft-versus-host-disease (GVHD) which occurs after bone marrow transplants (Giordano, et al. 2007). Paradoxically, one of one of the most useful and important early use of both human embryonic and mesenchymal stem cells transplantation is to suppress immune rejection of other cells.

    Adult stem cells may be interfering with the immune system by blocking t-cell function (Li Pira, et al., 2006). and preventing lymphocyte proliferation (Sudres, et al., 2006). In the meantime, several clinical studies have reported beneficial effects of adult mesenchymal stem cells in several conditions. Ringden, et al. (2006) treated 8 patients with mesenchymal stem cells and found that it reduced GVHD.

    Wise.

    References
    1. Giordano A, Galderisi U and Marino IR (2007). From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 211: 27-35. Mesenchymal Stem Cells (MSCs) are non-hematopoietic multi-potent stem-like cells that are capable of differentiating into both mesenchymal and non-mesenchymal lineages. In fact, in addition to bone, cartilage, fat, and myoblasts, it has been demonstrated that MSCs are capable of differentiating into neurons and astrocytes in vitro and in vivo. MSCs are of interest because they are isolated from a small aspirate of bone marrow and can be easily expanded in vitro. As such, these cells are currently being tested for their potential use in cell and gene therapy for a number of human diseases. Nevertheless, there are still some open questions about origin, multipotentiality, and anatomical localization of MSCs. In this review, we discuss clinical trials based on the use of MSCs in cardiovascular diseases, such as treatment of acute myocardial infarction, endstage ischemic heart disease, or prevention of vascular restenosis through stem cell-mediated injury repair. We analyze data from clinical trials for treatment of osteogenesis imperfecta (OI), which is a genetic disease characterized by production of defective type I collagen. We describe progress for neurological disease treatment with MSC transplants. We discuss data on amyotrophic lateral sclerosis (ALS) and on lysosomal storage diseases (Hurler syndrome and metachromatic leukodystrophy). A section of review is dedicated to ongoing clinical trials, involving MSCs in treatment of steroid refractory Graft Versus Host Disease (GVHD); periodontitis, which is a chronic disease affecting periodontium and causing destruction of attachment apparatus, heart failure, and bone fractures. Finally, we will provide information about biotech companies developing MSC therapy. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, Pennsylvania, USA. giordano@temple.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=17226788
    2. Li Pira G, Ivaldi F, Bottone L, Quarto R and Manca F (2006). Human bone marrow stromal cells hamper specific interactions of CD4 and CD8 T lymphocytes with antigen-presenting cells. Hum Immunol 67: 976-85. Bone marrow stromal cells (BMSCs) may inhibit T-cell functions in vitro and thus have been proposed as immunoregulators to control in vivo graft-versus-host disease (GVHD) in haploidentical hemopoietic stem cell transplants. To better investigate this phenomenon, we used a defined experimental system in which responding T cells are antigen-specific and devoid of alloreactivity against BMSC from a different subject. Thus, we established antigen-specific human CD4 and CD8 T-cell lines as the readout system. Antigen-dependent proliferation was reduced with both T-cell subsets cultured on confluent BMSCs, and also on confluent human skin fibroblasts (HSF) inhibited T-cell proliferation with similar efficiency. Morphological observations of the cocultures showed impairment of physical interactions between T-cell and antigen-presenting cells in the presence of BMSC, with lack of formation of antigen-dependent clusters of T cells and antigen-presenting cells (APCs). In contrast, no effects were seen with BMSC-conditioned medium. Since suppression was seen only with confluent mesenchymal cells, this phenomenon may not be relevant in vivo, where BMSCs are at low frequency. In addition, if the reported suppressive effect of BMSCs on GVHD in vivo is confirmed, a different in vitro system should be envisaged to better understand and exploit the underlying mechanism. Advanced Biotechnology Center, Genoa, Italy. lipira@email.it http://www.ncbi.nlm.nih.gov/entrez/q..._uids=17174746
    3. Sudres M, Norol F, Trenado A, Gregoire S, Charlotte F, Levacher B, Lataillade JJ, Bourin P, Holy X, Vernant JP, Klatzmann D and Cohen JL (2006). Bone marrow mesenchymal stem cells suppress lymphocyte proliferation in vitro but fail to prevent graft-versus-host disease in mice. J Immunol 176: 7761-7. Several reports have suggested that mesenchymal stem cells (MSCs) could exert a potent immunosuppressive effect in vitro, and thus may have a therapeutic potential for T cell-dependent pathologies. We aimed to establish whether MSCs could be used to control graft-vs-host disease (GVHD), a major cause of morbidity and mortality after allogeneic hemopoietic stem cell transplantation. From C57BL/6 and BALB/c mouse bone marrow cells, we purified and expanded MSCs characterized by the lack of expression of CD45 and CD11b molecules, their typical spindle-shaped morphology, together with their ability to differentiate into osteogenic, chondrogenic, and adipogenic cells. These MSCs suppressed alloantigen-induced T cell proliferation in vitro in a dose-dependent manner, independently of their MHC haplotype. However, when MSCs were added to a bone marrow transplant at a MSCs:T cells ratio that provided a strong inhibition of the allogeneic responses in vitro, they yielded no clinical benefit on the incidence or severity of GVHD. The absence of clinical effect was not due to MSC rejection because they still could be detected in grafted animals, but rather to an absence of suppressive effect on donor T cell division in vivo. Thus, in these murine models, experimental data do not support a significant immunosuppressive effect of MSCs in vivo for the treatment of GVHD. Biologie et Therapeutique des Pathologies Immunitaires Universite Pierre et Marie Curie/Centre National de la Recherche Scientifique Unite Mixte de Recherche 7087, Paris, France. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16751424
    4. Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L and Le Blanc K (2006). Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81: 1390-7. BACKGROUND: Mesenchymal stem cells (MSC) have immunomodulatory effects. The aim was to study the effect of MSC infusion on graft-versus-host disease (GVHD). METHODS: We gave MSC to eight patients with steroid-refractory grades III-IV GVHD and one who had extensive chronic GVHD. The MSC dose was median 1.0 (range 0.7 to 9)x10(6)/kg. No acute side-effects occurred after the MSC infusions. Six patients were treated once and three patients twice. Two patients received MSC from HLA-identical siblings, six from haplo-identical family donors and four from unrelated mismatched donors. RESULTS: Acute GVHD disappeared completely in six of eight patients. One of these developed cytomegalovirus gastroenteritis. Complete resolution was seen in gut (6), liver (1) and skin (1). Two died soon after MSC treatment with no obvious response. One of them had MSC donor DNA in the colon and a lymph node. Five patients are still alive between 2 months and 3 years after the transplantation. Their survival rate was significantly better than that of 16 patients with steroid-resistant biopsy-proven gastrointestinal GVHD, not treated with MSC during the same period (P = 0.03). One patient treated for extensive chronic GVHD showed a transient response in the liver, but not in the skin and he died of Epstein-Barr virus lymphoma. CONCLUSION: MSC is a very promising treatment for severe steroid-resistant acute GVHD. Center for Allogeneic Stem Cell Transplantation, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. olle.ringden@ki.se http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16732175
    Last edited by Wise Young; 07-01-2007 at 02:59 AM.

  3. #3
    Dear Wise-Young,

    thank you very much for your answer.
    My understanding of the therapy is that the fresh animal cells which will be injected are not attacked by the immune-system.
    When Niehans obtained parathyroid gland from a newborn ox and injected them intra-musculary into the patient, the cells failed to provoke an immune-reaction. The cells did survive for twenty-six years.
    You can read it:
    http://www.superqigong.com/articlesmore.asp?id=82

    It also was shown by a study in Germany that the cells find their way to the affected tissue/organ.
    Honestly I have to say I'am a bit confused now, because one person says "the cells are attacked by the immune-system", the other person says " no the cells will survive", the third person says " a part of the injected cells will suvive".
    It also said that Niehans sometimes used fetal cells. What is the advantage of fetal cells? Are they better than embryonic cells?
    Another point is this: If this therapy would not be effective than it wouldn't be allowed hiere in Germany.

    Regards,

    Fight_for_the_Cure_2007

  4. #4
    Quote Originally Posted by Fight_for_the_Cure_2007
    Dear Wise-Young,

    thank you very much for your answer.
    My understanding of the therapy is that the fresh animal cells which will be injected are not attacked by the immune-system.
    When Niehans obtained parathyroid gland from a newborn ox and injected them intra-musculary into the patient, the cells failed to provoke an immune-reaction. The cells did survive for twenty-six years.
    You can read it:
    http://www.superqigong.com/articlesmore.asp?id=82

    It also was shown by a study in Germany that the cells find their way to the affected tissue/organ.
    Honestly I have to say I'am a bit confused now, because one person says "the cells are attacked by the immune-system", the other person says " no the cells will survive", the third person says " a part of the injected cells will suvive".
    It also said that Niehans sometimes used fetal cells. What is the advantage of fetal cells? Are they better than embryonic cells?
    Another point is this: If this therapy would not be effective than it wouldn't be allowed hiere in Germany.

    Regards,

    Fight_for_the_Cure_2007
    Fight,

    In my experience, a majority of rats will reject xenografts transplanted from another species. It is true that when you transplant to the brain or spinal cord, the rejection is frequently delayed by 2-3 weeks, but it is invariably gone by 4 weeks. Many other scientists who are experienced with cell transplants share this perception of immune rejection.

    Inexperienced scientists who have reported immune-privilege of xenografts usually do one of three things that make their data suspect:
    1. Dye or particulate tracers. They use some kind of dye tracer or nanoparticle to mark their transplanted cells, instead of a genetic marker. When the transplanted cells die, the tracer is taken up by surrounding cells, leading to the misleading impression that labelled cells are present and may be neurons and astrocytes. These include experiments where scientists have used ferric nanoparticles, BRDU, fluorescent dyes, etc. In my opinin, none of this work is trustworthy.
    2. Did not wait long enough. The rejection take place over several weeks in the central nervous system. So, if you look at 2-3 weeks, there are often cells present. One tell-tale sign is if the cells are decreasing dramatically in number during the first three weeks. This is usually due to immune-rejection although some investigators believe that it is just the transplanted cells no surviving in the barren environment of the spinal cord.
    3. Use immune-compromised animals. Many investigators use immune-compromised animals for transplantation. This is particularly true of certain strains of mice. Rats tend to be more robust immunologically but there are variations amongs the strains as well. For example, we find that the Lewis rat is more immune tolerant, the Fischer is next, the Wistar is third, the Sprague-Dawley is the fourth, and the Long-Evans hooded rat is the most robust.

    When we study transplants in rats, we use cells from that have the gene for green fluorescent protein driven by the actin promoter. These cells express strong green fluorescence for as long as they live, even as they differentiate. When we first started transplant studies, we made the mistake of using various dyes as tracers and quickly found out that they are very misleading and the dyes are taken up by surrounding cells. In particular the Hoechst nuclear stain transfers readily form cell to cell. Particulate tracers are likewise taken up by other cells (particularly macrophages) when the cells containing the particles die.

    Some people use antibodies against the human nuclear stain when they are transplanting human cells into rat. This way, the human cells are stained while the rat cells are not. However, this method needs to carefully controllede with both negative and positive controls. In other words, alongside your experimental preparation, you need to also stain slides of tissues that you know have the cells and slides that don't have the cells, as positive and negative controls, to confirm that the method works and that you are not getting a false positive or a false negative.

    In any case, the survival of xenograft cells with immune rejection is against almost everything that we know. Even if we were to assume that the immature cells do not express antigens to turn on the immune system, it is likely that when the progeny (offsprings) of the cells will express antigens that will turn on the antigens. Immune rejection of foreign cells is a very powerful and effective mechanism in most animals with intact immune systems. Most scientists, including myself, are skeptical about claims that embryonic stem cells and mesenchymal stem cells can be transplanted and survive without HLA matching. Over 20 years of experience indicate that this is not true with bone marrow and umbilical cord blood cell transplants.


    Wise.

  5. #5
    Quote Originally Posted by Wise Young
    Fight,

    Most scientists, including myself, are skeptical about claims that embryonic stem cells and mesenchymal stem cells can be transplanted and survive without HLA matching.

    Wise.
    Dear,

    first of all thanks again for your answer, You claim that injection of mesenchymal stem cells will be rejected by the the human immune-system over time.
    To my knowledge there are so many studies supporting that mesenchymal stem cells will not be attacked by the human immune-system, therefore many doctors see these stem cell as a potent treatment agent for many disorders.
    Do you have a study which supports your claim?

    Regards,

    Fight_for_the_Cure_2007

  6. #6
    Quote Originally Posted by Fight_for_the_Cure_2007
    Dear,

    first of all thanks again for your answer, You claim that injection of mesenchymal stem cells will be rejected by the the human immune-system over time.
    To my knowledge there are so many studies supporting that mesenchymal stem cells will not be attacked by the human immune-system, therefore many doctors see these stem cell as a potent treatment agent for many disorders.
    Do you have a study which supports your claim?

    Regards,

    Fight_for_the_Cure_2007
    Fight,

    If you transplant autografts, they are not rejected. However, if you transplant cells from one person to another, they are rejected. That is the rule not the exception. Immune rejection is such a well-established phenomenon that nobody reports it anymore. The questions should be the other way around... What studies suggest that the cells are not rejected and how reliable are they?

    In any case, let me delve back deep into the history of graft rejection. In 1955, Sir Peter Medawar first demonstrated that allografts are rejected when transplanted into different parts of the body but at different times and probably through different mechanisms. One of the most interesting is the rejection of cells transplanted into the eye (Source). Apparently, there is immune rejection in the eye.

    Bone marrow stem cells have been used for many years to treat hematopoietic disorders. But it is also well know that unless one has perfect 6 out of 6 HLA antigen match and preferably from a relative, the cells will be rejected and also will attack the host, a condition called graft-versus-host disease. This is why there are huge repositiories of bone marrow donors (5 million around the world) who have contributed blood that is put onto a database for matching purposes and are called in to donate bone marrow or blood for stem cells.

    Several years ago, mesenchymal stem cells were discovered in bone marrow and found to differentiate into cartilage, tendon, fat, and other cells. They have been claimed to be immune-privileged and "seem to be available" for HLA-independent cell transplantation (see Niemeyer, 2006 - attached). Pluritstem (Source) has claimed that their mesenchymal stem cells obtained from placental cells posess immune privilege characteristics. I have met several groups in China that are study mesenchymal stem cell therapies being given to people in clinical trials for stroke and other conditions. They are growing the cells from cell-lines.

    I am watching these trials with a great deal of interest and hope. Nevertheless, I must say that I am skeptical. In my experience with allogenic transplants and xenograft in animals, they are invariably been rejected. I have never seen the phenomena that these people describe, except in the case when they have created tumor cells. By the way, tumor cells possess some mechanisms that allow them to escape detection by the immune system and grow inexorably to kill the cell. That is why I am worried about all these reports of cells that are immune-privileged.

    By the way, I am perfectly willing to accept that the stem cell itself may be immune-privileged and even anti-immune or anti-inflammatory. However, if it is to act as a stem cell, it needs to be shown that the progeny (the offsprings) of the stem cell are also immune privileged. Now, in the case of Geron, where they have created oligodednroglial precursor cells from human embrynic stem cells, I believe that they are planning to do some initial immune suppression of the patients in their clinical trial. In any case, that is what the clinical trials are for.

    Wise.

  7. #7
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    if you transplant cells from one person to another they are rejected....
    dr.huang has knowledge about this issue?
    • Dum spiro, spero.
      • Translation: "As long as I breathe, I hope."

  8. #8
    Please read this article:

    http://www.hms.harvard.edu/news/pres...ne_marrow.html

    It is purely speculative, but if they would give the patient more mesenchymal stem cells than his condition would probably much better. Thats the problem of human allograft transplantation, the donor cells are not enough and are limited. Taking donor cells from animals would overcome such problems.


    Fight_for_the_Cure_2007

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