Understanding Scleroderma stem cell transplant


 Administrator    28 Oct 2019 : 07:05

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All you need to know before your scleroderma stem cell transplant

Prior to undertaking a scleroderma stem cell transplant it is important to get up-to-date with what is involved in the procedure and why recent research has shown the tremendous benefits that this form of treatment has to offer.

Overview

Scleroderma comes from the Greek words skleros (hard) and derma (skin) and means a disease that results in progressive skin hardening and damage to other structures. Scleroderma is one component of systemic sclerosis, a body-wide connective tissue disease that also involves skin, subcutaneous tissue, muscles, and organs.

It is characterized by the excessive deposit of collagen and other large molecules into the skin and multiple internal organs, with scarring and damage to small blood vessels. The immune system is damaged, and scleroderma is considered an autoimmune disease whereby the body attacks itself.

Systemic sclerosis is a complex and multifaceted disease with clinical forms ranging from skin involvement only, usually areas like the forearm, hands, and fingers, to forms with diffuse skin sclerosis and severe, progressive internal organ involvement. Some skin areas affected might be the face and neck.

One form of skin involvement is called the CREST syndrome. This relates to: 

  • Calcium elevation
  • Raynaud phenomenon (severe blood vessel spasms of the fingers or toes)
  • Esophageal dysmotility 
  • Sclerodactyly (fingers that become elongated with skin tightness)
  • Telangiectasias (tiny broken capillaries)

although not all of those signs are needed for the disorder to be called CREST.

Diffuse cutaneous systemic sclerosis refers to skin thickening of the trunk, extremities, and involvement of the face. Other organs that can be affected are the stomach, kidneys, heart, muscles, hormone-producing organs, and bladder.

Causes of Scleroderma

The exact cause of systemic sclerosis is not known but it does not appear to be inherited, although a genetic predisposition probably plays a role in its development. Environmental factors may trigger or accelerate the development of systemic sclerosis if the person has the genetic propensity [1,2,3,4,5]. These include the following:

Silica exposure

  • Solvent exposure such as vinyl chloride, trichloroethylene, epoxy resins, benzene, and carbon tetrachloride
  • Radiation exposure or radiotherapy
  • Exposure to pembrolizumab (a treatment for melanoma)
  • Herpesvirus 5, Parvovirus B19, and cytomegalovirus may also trigger the disease [6]

Skin manifestations

Skin signs and symptoms of scleroderma are as follows:

Progressive skin tightness and hardness usually preceded by swelling and puffiness that do not respond to drugs to induce water excretion from the tissues—diuretics.

  • Skin hardness that initially affects the fingers (sclerodactyly) and extends towards the hands
  • Tightening of the skin in the face
  • The fingers develop an ulcer, loss of creases, damaged joints, and reduced hair growth
  • Pigment changes in the skin, either lightening or darkening
  • Diffuse itching

Blood Vessel Involvement

Raynaud phenomenon occurs initially in 70% of patients with systemic sclerosis; 95% eventually develop it as the disease progresses but may precede the systemic disease by many years. The female-to-male ratio is 4:1, and it starts in adolescence.


Other vascular manifestations of systemic sclerosis include:

  • Healing depressed ulcers on fingertips
  • Large fingertip ulcers which might end up amputated
  • Cutaneous and mouth spider veins
  • Large vessels can narrow and lead to a heart attack.

Gastrointestinal (GI) manifestations

 There is a lot of information relating to GI manifestations as they relate to scleroderma. GI findings are:

  • Gastroesophageal reflux caused by reduced movement of the esophagus and weakened lower esophageal sphincter (LES) which may lead to hoarseness, difficulty swallowing and aspiration which could lead to pneumonia
  • Upset stomach, bloating, and early satiety
  • Intestinal narrowing creating a partial obstruction
  • Constipation and/or diarrhea from bacterial overgrowth that may lead to a malabsorption problem
  • Fecal incontinence
  • Malnutrition
  • Chronic iron deficiency anemia from tiny leaks of blood

Respiratory Problems consist of the following:

  • Progressive shortness of breath
  • Chest pain
  • Dry, persistent cough

Musculoskeletal symptoms

Musculoskeletal complaints may include the following:


  • Joint aches
  • Muscle aches
  • Loss in joint range of motion and joint deformities
  • Tendonitis
  • Numbness of fingers or toes
  • Muscle weakness

Cardiac manifestations

Cardiac signs and symptoms in severe systemic sclerosis include the following:

Heart failure due to scarred heart muscle

  • Palpitations, irregular heartbeats, and lightheadedness and passing out due to arrhythmias
  • Feet swelling from heart failure

Kidney manifestations

Renal signs and symptoms include the following:

  • Hypertension
  • Kidney failure

Genitourinary manifestations

Patients may have the following:

  • Erectile dysfunction
  • Bladder scarring and frequency or urgency of urination
  • Painful sex for women
  • Vaginal narrowing, dryness, and pain from scarring

Patients may also present with the following signs and symptoms:

  • Loosening of teeth
  • Increased risk for tongue cancer
  • Decreased size of mouth opening
  • Blindness caused
  • Facial pain or weakness
  • Headache
  • Stroke
  • Fatigue
  • Weight Loss
  • Loss of appetite

How to Diagnose Scleroderma

There are a number of ways that scleroderma may be diagnosed. It is most often diagnosed following laboratory testing. Laboratory testing may include the following:

  • Complete blood cell count (CBC)
  • Serum muscle enzyme levels
  • Erythrocyte sedimentation rate
  • Serum CXCL4 level
  • N-terminal pro-brain natriuretic peptide
  • Autoantibody assays

Other testing methods:

X-rays (abdomen, chest, hands, jaw)

Endoscopy of the esophagus and GI tract

Colonoscopy

High-resolution CT

Lung function studies

Electrocardiograms (ECGs)

Holter monitoring for 24-hours to detect arrhythmias

To date, treatment of SSc patients is for symptom relief since there is no cure. Drugs aimed at alleviating Raynaud’s phenomenon, gastro-oesophageal reflux, pain, and immunosuppressants (methotrexate, mycophenolate mofetil, and cyclophosphamide), or organ transplantation in case of severe heart-lung involvement [7]. There have been new drugs for the treatment of PAH [8], but the scleroderma person’s prognosis and mortality have not changed in the last 40 years [9].

Stem Cell Treatment and Scleroderma

Mesenchymal stem cells (MSCs) are a promising therapeutic approach primarily due to their anti-fibrotic (anti-scarring), angiogenic (vessel growth), and immune-stimulating or modulating capacities. They act on the different processes that are dysregulated in the disease. Recently, the therapeutic effectiveness of MSCs has been demonstrated in different preclinical animal trials and currently in phase I human trials. Both foreign (allogenic) and autologous (self) derived stem cells from bone marrow, or fat tissue are being evaluated. The reason for using allogenic MSCs in Scleroderma is because it is an autoimmune disease, and’ self’ MSCs may be already damaged and not work as well.

MSCs are ‘generic’ adult cells that have the capacity to differentiate into many different but specific cell types and have been identified in the bone marrow (BM), adipose, umbilical cord blood, placenta, and dental pulp [9,10].

How does a stem cell transplant work in regards to scleroderma?

In Scleroderma stem-cell transplantation, the main functions of MSCs are thought to be anti-inflammatory to counteract the messed up immune system, anti-fibrotic by reducing the excessive collagen deposition into the skin and internal organs that cause hardening, and pro-vessel forming to fight the vessel- damaging effects of scleroderma [11,12,13]

One study comparing adipose-derived stem cells (ADSC) from a donor to those collected from the person with scleroderma showed that the function and results from both types are identical. The only difference was the reduced proliferation and migration capacity of ADSC from scleroderma patients [14].

In a study conducted by Scuderi et al., six scleroderma patients were treated with ASC in affected skin areas (face or limbs) combined with the injection of acid hyaluronic, with a good reduction of skin thickness and no local complications [15].

In 2011, a German team published four more cases of refractory Systemic Scleroderma (SSc) treated with allogeneic bone marrow (BM)-MSC [16]. At 18-month follow-up, four of the five patients had an improvement in overall skin score for disease, digital ulcers or distal limb necrosis with no major complications.

Can Stem Cells Cure Scleroderma?

As the recently conducted trials clearly show, stem cell transplant treatment for scleroderma continues to be a great reason for optimism. As the effectiveness of this treatment method continues to gain traction from various clinical studies, finally scleroderma sufferers can look forward to a brighter future.

How much does a stem cell transplant cost? 

Prices for treatment with stem cells varies significantly based on the individual patient’s needs, the location of the treatment center, and other factors. The treatment center that you intend to visit should be contacted for all matters regarding pricing. 

https://stemaidinstitute.eu/contact-us

How long does a stem cell transplant take? 

The length of treatment will vary considerable for a stem cell transplant and this will be based on a number of individual factors relating to the severity of the scleroderma experienced by the patient attending a clinic.

References

  1. Dospinescu P, Jones GT, Basu N. Environmental risk factors in systemic sclerosis. Curr Opin Rheumatol. 2013 Mar. 25(2):179-83.

  2. Nietert PJ, Sutherland SE, Silver RM, Pandey JP, Knapp RG, Hoel DG. Is occupational organic solvent exposure a risk factor for scleroderma?. Arthritis Rheum. 1998 Jun. 41(6):1111-8.

  3. Marie I, Gehanno JF, Bubenheim M, Duval-Modeste AB, Joly P, Dominique S. Prospective study to evaluate the association between systemic sclerosis and occupational exposure and review of the literature. Autoimmun Rev. 2014 Feb. 13(2):151-6.

  4. Rubio-Rivas M, Moreno R, Corbella X. Occupational and environmental scleroderma. Systematic review and meta-analysis. Clin Rheumatol. 2017 Mar. 36 (3):569-582.

  5. Barragán-Martínez C, Speck-Hernández CA, Montoya-Ortiz G, Mantilla RD, Anaya JM, Rojas-Villarraga A. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS One. 2012. 7(12):e51506.

  6. Moroncini G, Mori S, Tonnini C, Gabrielli A. Role of viral infections in the etiopathogenesis of systemic sclerosis. Clin Exp Rheumatol. 2013 Mar-Apr. 31(2 Suppl 76):3-7.

  7. Launay D, Savale L, Berezne A, Le Pavec J, Hachulla E, Mouthon L, Sitbon O, Lambert B, Gaudric M, Jais X, Stephan F, Hatron PY, Lamblin N, Vignaux O, Cottin V, Farge D, Wallaert B, Guillevin L, Simonneau G, Mercier O, Fadel E, Dartevelle P, Humbert M, Mussot S, Working Group on Heart/Lung transplantation in systemic sclerosis of the French Network on Pulmonary H (2014) Lung and heart-lung transplantation for systemic sclerosis patients. A monocentric experience of 13 patients, review of the literature and position paper of a multidisciplinary Working Group. Presse Med 43 (10 Pt 2):e345-363. doi:10.1016/j.lpm.2014.01.020

  8. Sobanski V, Launay D, Hachulla E, Humbert M (2016) Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH). Curr Rheumatol Rep 18 (2):10. doi:10.1007/s11926-015-0560-x

  9. Elhai M, Meune C, Avouac J, Kahan A, Allanore Y (2012) Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford) 51 (6):1017-1026. doi:10.1093/rheumatology/ker269

  10. . da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. (2006) 119:2204–13. doi: 10.1242/jcs.02932

  11. Cras A, Farge D, Carmoi T, Lataillade JJ, Wang DD, Sun L. Update on mesenchymal stem cell-based therapy in lupus and scleroderma. Arthritis Res Ther. (2015) 17:301. doi: 10.1186/s13075-015-0819-7

  12. Maria AT, Maumus M, Le Quellec A, Jorgensen C, Noel D, Guilpain P. Adipose-derived mesenchymal stem cells in autoimmune disorders: state of the art and perspectives for systemic sclerosis. Clin Rev Allergy Immunol. (2017) 52:234–59. doi: 10.1007/s12016-016-8552-9

  13. Peltzer J, Aletti M, Frescaline N, Busson E, Lataillade JJ, Martinaud C. Mesenchymal stromal cells based therapy in systemic sclerosis: rational and challenges. Front Immunol. (2018) 9:2013. doi: 10.3389/fimmu.2018.02013

  14. Griffin, M., Ryan, C. M., Pathan, O., Abraham, D., Denton, C. P., & Butler, P. E. (2017). Characteristics of human adipose derived stem cells in scleroderma in comparison to sex and age matched normal controls: implications for regenerative medicine. Stem cell research & therapy, 8(1), 23. doi:10.1186/s13287-016-0444-7

  15. Scuderi N, Ceccarelli S, Onesti MG, Fioramonti P, Guidi C, Romano F, Frati L, Angeloni A, Marchese C (2013) Human adipose-derived stromal cells for cell-based 62 therapies in the treatment of systemic sclerosis. Cell transplantation 22 (5):779-795. oi:10.3727/096368912X639017



  16. Keyszer G, Christopeit M, Fick S, Schendel M, Taute BM, Behre G, Muller LP, Schmoll HJ (2011) Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: report of five cases. Arthritis and rheumatism 63 (8):2540-2542. doi:10.1002/art.30431




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