What are Auto-Immune diseases?

Autoimmune Diseases (ADs) represent a heterogeneous group of disorders with genetic, environmental
and individual etiological factors. ADs can be broadly divided into systemic and organ-specific
autoimmune disorders, depending on the principal clinico-pathologic features of each disease.
The etiopathogenesis of systemic ADs has previously been attributed to T cell deficiencies, polyclonal
B cell activation, macrophage dysfunction and environmental factors. ADs affect organs and tissues
such as blood vessels, connective tissues, thyroid, pancreas, joints, muscles, and skin.
Criteria for ADs:
1. Direct evidence from transfer of pathogenic antibodies or pathogenic T cells
2. Indirect evidence based on reproduction of the autoimmune disease in experimental animals
3. Circumstantial evidence from clinical clues
(1) Rheumatological Auto-Immune diseases –
• Systemic sclerosis
• Necrotizing vasculitis
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Antiphospholipid antibody syndrome
• Severe\ uncontrollable cryoglobulinaemia
(2) Neurological Auto-Immune diseases –
• Multiple sclerosis
• Myasthenia gravis
(3) Haematological Auto-Immune diseases –
• Severe refractory autoimmune thrombopenia
• Autoimmune haemolytic anaemia
• Immune neutropenia
(4) Other Auto-Immune diseases –
• Infammatory bowel disease (chrons’ disease, ulcerative colitis)
• Autoimmune diabetes mellitus

What are stem cells and how they’re changing the way ADs are treated?

Stem cells are characterized by their capacity for self-renewal, multilineage differentiation,
proliferation, mobilization, and homing. Stem cells can be divided into two main groups:
• embryonic stem cells (ESCs) and,
• adult stem cells (ASCs)
Stem cell transplantation has been recommended for use in the treatment of AD because it provides
immunosuppressive and immunomodulatory effects. Stem cell therapy can destroy the defective
immune system, renew the lymphatic system, reduce the disease activity, and lead to long-term
remission of AD.
AD patients who were once resistant to conventional therapy, following therapy, are shown to become
sensitive to the same conventional therapy, highlighting the immunomodulatory properties of stem cell
Sources of Stem Cells
Bone marrow or, peripheral blood stem cells can be used. It has been clearly documented that
autologous peripheral blood stem cells lead to a faster and more complete recovery. Peripheral blood
stem cells are preferred to bone marrow derived stem cells for autologous transplants. However bone
marrow derived stem cells contain fewer mature autoreactive T cells which may prove to be important
if purging techniques fail to remove enough such cells.
Types of Stem cell therapies for ADs and their Advantages:
• Hematopoietic stem cell therapy (HSC therapy)
• Mesenchymal stem cell therapy (MSC therapy)
• Adipose tissue-derived Mesenchymal stem cells and,
• Gene transfected stem cell therapy
MSC have immunomodulatory properties and immunosuppressive effects on MHC-mismatched
lymphocytes proliferation by inhibiting naïve, memory and activated T cells, B cell, Natural Killler
cells and dendritic cells. This concept is completely different from HSCT in that the patient does not
need to be immunosuppressed prior to MSC transplantation, and that the therapeutic effect is
considered to be delivered in the inflamed organ due to homing of MSC with a relatively short lived
Adipose tissue-derived MSC (AT-MSC) are becoming an alternative source of MSC for therapeutic
applications because adipose tissues are abundant, easily accessible, easily obtainable with little patient
discomfort and large amounts of AT-MSC can be easily obtained

Current trend in employing Stem cell therapy for ADs:

Most clinical studies based on stem cell therapy in AD patients use HSCT mobilized from Bone
Marrow to peripheral blood. There is no significant difference in the transplantation protocols used for
different diseases.
Choosing patients in the initial stages of the disease appears to be safer and more effective. However,
this procedure involves the risk of exposing patients who may respond well to conventional therapy to
new non-standard treatment methods
Issues faced with use of SCT:
Relapse could be caused by contamination of the graft with autoimmune cells.
The contamination of grafts by auto-reactive lymphocytes can be controlled using pure cell lines
expanded in the laboratory, which would also increase the number of stem cells available for the
It is known that embryonal stem cells (ESCs) have a greater capacity for differentiation and less
immunogenetic potential than adult stem cells (ASCs). Nevertheless, ESCs could be used as an
alternative when there is a high risk of immunological rejection with ASC therapy. However, the use of
ESCs remains limited and far from being a therapeutic alternative for such patients due to the risk of
the development of teratomas and the ethical issues involving the use of this procedure.
How to combat these issues:
A mixed approach involving the combination of genetic transference with cellular therapy is able to
increase the therapeutic potency of stem cell transplantation. It permits the correction of genetic
anomalies and helps in the control of disease by increasing the expression of regulatory elements.



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