Rheumatoid Arthritis Stem Cell Treatment

Rheumatoid Arthritis and Stem Cell Therapy

Stem Cell Treatment Rheumatoid ArthritisRheumatoid Arthritis and Stem Cell Therapy
Rheumatoid arthritis (RA), is a chronic system wide inflammatory disorder that may affect many tissues and organs however RA primarilly attacks the joints.

Stem Cell Treatmenst for Rheumatoid Arthritis is available. The Disease process often leads to the decay of articular cartilage and ankylosis of the joints. Rheumatoid Arthritis can also produce diffuse inflammation in the lungs, pericardium, pleura, and sclera, and also nodular lesions, most common in subcutaneous tissue.

Although the cause of Rheumatoid Arthritis is unknown, autoimmunity plays a pivotal role in both its chronic status and progression. RA is considered a systemic autoimmune disease.




Stem Cell Treatment Rheumatoid Arthritis

Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications.
Yi T, Song SU.
2012 Feb;35(2):213-21. Epub 2012 Feb 28.

Clinical Research Center, Inha Research Institute, Inha University School of Medicine, Incheon, 400-712, Korea.

Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from most adult tissues, including bone marrow, adipose, liver, amniotic fluid, lung, skeletal muscle and kidney. The term MSC is currently being used to represent both mesenchymal stem cells and multipotent mesenchymal stromal cells. Numerous reports on systemic administration of MSCs leading to functional improvements based on the paradigm of engraftment and differentiation have been published. However, it is not only difficult to demonstrate extensive engraftment of cells, but also no convincing clinical results have been generated from phase 3 trials as of yet and prolonged responses to therapy have been noted after identification of MSCs had discontinued. It is now clear that there is another mechanism by which MSCs exert their reparative benefits. Recently, MSCs have been shown to possess immunomodulatory properties. These include suppression of T cell proliferation, influencing dendritic cell maturation and function, suppression of B cell proliferation and terminal differentiation, and immune modulation of other immune cells such as NK cells and macrophages. In terms of the clinical applications of MSCs, they are being tested in four main areas: tissue regeneration for cartilage, bone, muscle, tendon and neuronal cells; as cell vehicles for gene therapy; enhancement of hematopoietic stem cell engraftment; and treatment of immune diseases such as graft-versus-host disease, rheumatoid arthritis, experimental autoimmune encephalomyelitis, sepsis, acute pancreatitis and multiple sclerosis. In this review, the mechanisms of immunomodulatory effects of MSCs and examples of animal and clinical uses of their immunomodulatory effects are described.
Haematopoietic stem cell gene therapy as a treatment for autoimmune diseases.

Mol Pharm. 2011 Jul 6;

Authors: Alderuccio F, Nasa Z, Chung J, Ko H, Chan J, Toh BH

A key function of the immune system is to protect us from foreign pathogens such as viruses, bacteria and parasites. However, it is also important in many other aspects of human health such as cancer surveillance, tissue transplantation, allergy and autoimmune disease. Autoimmunity can be defined as a chronic immune response that targets self-antigens leading to tissue pathology and clinical disease.

As a group of diseases that include type 1 diabetes, multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus, there are no effective cures and treatment is often based on long-term broad-spectrum immunosuppressive regimes.

While a number of strategies aimed at providing disease specific treatments are being explored, one avenue of study involves the use of haematopoietic stem cells to promote tolerance. In this manuscript, we will review the literature in this area but in particular examine the relatively new experimental field of gene therapy and haematopoietic stem cells transplantation as a molecular therapeutic to combat autoimmune disease.

PMID: 21732672 [PubMed - as supplied by publisher]

Mesenchymal stem cells: Re-establishing immunological tolerance in autoimmune rheumatic diseases.

Arthritis Rheum. 2011 Jun 6;

Authors: Macdonald GI, Augello A, De Bari C

Immunological tolerance is critical in preventing autoimmune disease and maintaining immune homeostasis. Increased understanding regarding cytokine networks led to the development of neutralizing antibodies against TNF alpha, IL-1 and IL-6 signalling in the treatment of rheumatoid arthritis (RA). However, there remains an unmet need given the significant number of patients not achieving remission nor responding to these drugs. Mesenchymal (stromal) stem cells (MSCs) are promising tools for the repair of damaged joint tissues such as cartilage, bone and tendons.

They also have potent anti-inflammatory and immunomodulatory properties both in vitro and in vivo [1]. Research into MSC therapy for Crohn's disease, type I diabetes, graft-versus-host disease (GvHD) and multiple sclerosis continues apace with phase II/III trials ongoing. There have been conflicting reports regarding their effects in the autoimmune rheumatic diseases, particularly in the collagen-induced arthritis mouse model of RA [2-8].

Conversely, promising results in patients with systemic lupus erythematosus (SLE) were recently reported [9] even in the face of conflicting results in murine models of SLE. In this article we will examine MSCs as a possible cellular therapy for RA, SLE and systemic sclerosis (SSc) and critically review possible reasons for conflicting results in the literature. We will also address whether MSC dysfunction could play a role in the aetiopathogenesis of these conditions.

Finally, we will examine the possible mechanisms of MSCs at a cellular level including the effects on regulatory T (Treg) cells and type 17 T helper (Th17) cell populations.

PMID: 21647863 [PubMed - as supplied by publisher]

Autologous hematopoietic stem cell transplantation in autoimmune diseases.

Expert Rev Hematol. 2009 Dec;2(6):699-715

Authors: Annaloro C, Onida F, Lambertenghi Deliliers G

The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies.

Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system.

Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted.

Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys.

In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy.

Stem Cell Therapy Rheumatoid Arthritis

Stem Cell Therapy for Rheumatic Disease

Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus.

A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia.

Therefore, a sustained complete remission seems to be within the reach of autografting in some autoimmune diseases; in others, the indications, risks and benefits of autografting need to be better defined. Consequently, the search for new drugs should also be encouraged.

Related Articles Guidelines for Cervical Cancer Screening in Immunosuppressed Women Without HIV Infection. J Low Genit Tract Dis. 2019 Apr;23(2):87-101 Authors: Moscicki AB, Flowers L, Huchko MJ, Long ME, MacLaughlin KL, Murphy J, Spiryda LB, Gold MA Abstract EXECUTIVE SUMMARY: The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available. RESULTS: Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer. RECOMMENDATIONS: The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population. PMID: 30907775 [PubMed - in process]

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