Crohn’s disease is a type of inflammatory bowel disease that occurs in half a million people in North America. It may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms, including abdominal pain, bloating, diarrhea (which may be bloody if inflammation is at its worst), vomiting (can be continuous), or weight loss. Skin rashes and arthritis can also occur. Crohn’s disease has a genetic component, but it is an auto-immune disease in which the person’s own immune system attacks the gastrointestinal tract possibly directed at microbial antigens. The terminal ileum is the part of the bowel most often affected in this disease. Treatment often includes immune-suppressant therapy with steroids. Antibiotics and anti-inflammatories are also used extensively. In Europe, stem cells are used commonly to treat Crohn’s. Research is ongoing to evaluate the effects of stem cells on auto-immune conditions. The Journal of Translational Research reports that “non-expanded SVF cells have been used successfully in accelerating healing of Crohn’s fistulas” Read more…

     We use a specific SVF deployment protocol that attempts to utilize the potential immune-modulatory, anti-inflammatory, and regenerative properties of SVF (rich in mesenchymal stem cells and growth factors). SVF is deployed systemically and may require repeat dosing. This is done as an outpatient at the time of SVF harvesting and procurement. The entire cellular surgical procedure takes approximately three hours.

Crohn’s Disease Call to Action

     We care about our Crohn’s patients and take pride in the time we provide to our patients to deploy the best protocols to help our patients achieve their goals. By filling out Confidential Candidate Application, we will answer all of the questions and concerns you may have about our protocols for Crohn’s disease.

 
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Cell Surgical Network Study for Stromal Vascular Fraction Registered by ClinicalTrials.gov

Rancho Mirage, CA (PRWEB) October 14, 2013

Clinicaltrials.gov, a service of the U.S. National Institutes of Health has registered on their public site an IRB approved safety study from the Cell Surgical Network, Inc.. This study is available for patients with various degenerative and inflammatory conditions to undergo Stromal Vascular Fraction deployment for the evaluation and for the advancement of future stem cell therapy procedures. Stromal Vascular Fraction is rich in autologous adipose derived stem cells and growth factors.

Stromal Vascular Fraction (SVF) is obtained by lipo-harvesting, procurement, and lipo-transfer as a same day operative procedure to provide therapy to patients with various degenerative and inflammatory diseases. Patients must be 16 years or older, male or female and have a degenerative disease or inflammatory disease that meets criteria for treatment under the IRB which includes: Arthritis, Auto-immune disease, COPD, Cardiomyopathy, Peyronies Disease, Interstitial Cystitis, Erectile Dysfunction, and Neurodegenerative disease such as Parkinson’s, ALS, Neuropathy. Patients must be healthy enough to tolerate a local anesthetic, must not have active cancer or infections.

Dr. Elliot Lander, and Dr. Mark Berman, founders of the Cell Surgical Network Inc. will conduct the study: “Ever since our inception, it’s been our goal to maintain transparency during our investigations. With a closed surgical procedure we can provide effective safety studies and evolve good empirical data that will allow us and others to ultimately refine our protocols,” says Dr. Berman.

The purpose of the safety study is to evaluate for any adverse effects that may be related to the administration and reception of autologous adipose derived stromal vascular fraction (SVF). Secondarily, the study monitors the results of subjective and objective findings as it applies to the non-blinded deployment of autologous SVF for various inflammatory and/or degenerative conditions including select orthopedic, neurologic, urologic and cardio-pulmonary conditions. SVF deployments include intra-venous, intra-articular, and soft tissue injections.

Outcome measures will include the number of participants with adverse events related to either SVF deployment or the lipo-harvesting procedure. Interested patients should contact the treatment center by phone: 800-231-0407 or via email: info(at)cellsurgicalnetwork(dot)com

About Cell Surgical Network:

The affiliates of the Cell Surgical Network (CSN) are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions. The Cell Surgical Network was founded nearly two years after the formation of the California Stem Cell Treatment Center (founded in 2010). Affiliate members are generally made up of multi-state and international teams of multidisciplinary physicians in order to best assess and provide care for our patients. The Cell Surgical Network emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine.

 
Stem cells in intestinal inflammatory diseases.

Ter Arkh. 2010;82(2):38-43.

Use of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases.
[Article in Russian] Lazebnik LB, Konopliannikov AG, Kniazev OV, Parfenov AI, Tsaregorodtseva TM, Ruchkina IN, Khomeriki SG, Rogozina VA, Konopliannikova OA.
Abstract

AIM:
to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID).

SUBJECTS AND METHODS:
Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn’s disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn’s disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2) x 10(8) tells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion.

RESULTS:
A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comporison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only.

CONCLUSION:
The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

 
Severe anti-TNF refractory Crohn disease.

Blood. 2010 Dec 23;116(26):6123-32. Epub 2010 Sep 13.

Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up.
Burt RK, Craig RM, Milanetti F, Quigley K, Gozdziak P, Bucha J, Testori A, Halverson A, Verda L, de Villiers WJ, Jovanovic B, Oyama Y. Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. rburt@northwestern.edu

Abstract
We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti-tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m(2)) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34(+) selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.
Comment in
Blood. 2010 Dec 23;116(26):5790-1.

 
Risk reduction in ulcerative colitis relapse.

Eksp Klin Gastroenterol. 2010;(3):5-10.

Transplantation of allogeneic mesenchymal stem cells from the bone marrow increases duration of remission and reduces the risk of ulcerative colitis relapse.
[Article in Russian] Lazebnik LB, Kniazev OV, Parfenov AI, Ruchkina IN, Rogozina VA, Konopliannikov AG.
Abstract

The first results of allogeneic mesenchymal stem cells from the bone marrow transplantation to patients with ulcerative colitis demonstrated improved clinical course. We found an increasing in the duration of remission in patients with chronic recurrent and continuous recurrent course of ulcerative colitis. Also it was noted reducing the risk of relapse, and reducing the frequency of hospital admissions compared with medication therapy with only 5 aminosalicylic acid and glucocorticosteroid.

PMID: 20496783 [PubMed – indexed for MEDLINE]

 
Stem cells and complex perianal fistula.

Dis Colon Rectum. 2009 Jan;52(1):79-86.

Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial.

Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M.
Source
Department of Surgery and Cell Therapy, La Paz University Hospital, Universidad Autónoma de Madrid, Madrid, Spain. damian.garcia@uam.es
Abstract

PURPOSE:
The feasibility and safety of stem cell-based therapy with expanded adipose-derived stem cells (ASCs) has been investigated in a phase I clinical trial. The present study was designed as a phase II multicenter, randomized controlled trial to further investigate the effectiveness and safety of ASCs in the treatment of complex perianal fistulas.

METHODS:
Patients with complex perianal fistulas (cryptoglandular origin, n = 35; associated with Crohn’s disease, n = 14) were randomly assigned to intralesional treatment with fibrin glue or fibrin glue plus 20 million ASCs. Fistula healing and quality of life (SF-12 questionnaire) were evaluated at eight weeks and one year. If healing was not seen at eight weeks, a second dose of fibrin glue or fibrin glue plus 40 million ASCs was administered.

RESULTS:
Fistula healing was observed in 17 (71 percent) of 24 patients who received ASCs in addition to fibrin glue compared with 4 (16 percent) of 25 patients who received fibrin glue alone (relative risk for healing, 4.43; confidence interval, 1.74-11.27); P < 0.001). The proportion of patients with healing was similar in Crohn’s and non-Crohn’s subgroups. ASCs were also more effective than fibrin glue alone in patients with a suprasphincteric fistulous tract (P = 0.001). Quality of life scores were higher in patients who received ASCs than in those who received fibrin glue alone. At one year follow-up, the recurrence rate in patients treated with ASCs was 17.6 percent. Both treatments were well tolerated.

CONCLUSION:
Administration of expanded ASCs (20 to 60 million cells) in combination with fibrin glue is an effective and safe treatment for complex perianal fistula and appears to achieve higher rates of healing than fibrin glue alone.

 
Microcirculation and tissue regeneration.

Gastroenterology. 2007 Mar;132(3):944-54. Epub 2006 Dec 19.

Nonmyeloablative stem cell therapy enhances microcirculation and tissue regeneration in murine inflammatory bowel disease.
Khalil PN, Weiler V, Nelson PJ, Khalil MN, Moosmann S, Mutschler WE, Siebeck M, Huss R.
Department of Surgery, Klinikum Innenstadt, Ludwig-Maximilians-Universität of München, Munich, Germany. philipe.khalil@med.uni-muenchen.de

Abstract

BACKGROUND AND AIMS:
Reduced microcirculation has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Stem cells or endothelial progenitor cells are thought to contribute to tissue regeneration through neoangiogenesis or vasculogenesis in ischemia- or inflammatory-related diseases. We therefore hypothesized that adult stem cells facilitate epithelial repair in IBD.

METHODS:
Moderate-severe colitis in mice was induced by dextran sulfate sodium (DSS) and 2.0 x 10(6) immortalized CD34(-) stem cells infused twice via the tail vein during an observation period of 35 days in a nonmyeloablative setting.

RESULTS:
Here, we demonstrate that adult stem cells home to the damaged digestive tract in the large intestine and facilitate mucosal repair in moderate-severe colitis. Nonmyeloablative stem cell therapy resulted in increased survival in severe colitis (P < .0001). Moreover, clinical activity and histologic evaluation of the colitis severity score were reduced significantly in moderate (P = .0003 or P = .03) and severe (P < .0001 or P < .03) colitis after 35 days, in addition to the DSS-induced shortening of colon length (P = .002 and P < .0002). Genetically marked stem cells were detected predominantly in the submucosa of the damaged colon epithelium. Epithelial repair in experimental IBD was mediated either by induction of improved vasculogenesis or by the differentiation of the transplanted stem cells into endothelial cells, as demonstrated by the promotion of Tie2 activity in the infused cells at the site of the damaged mucosa.

CONCLUSIONS:
Our findings indicate that systemically administered adult stem cells respond to an adequate tissue lesion in murine IBD by enhancing microcirculation, resulting in accelerated tissue repair.
Comment in
Gastroenterology. 2007 Mar;132(3):1171-3.

 
Haemopoietic stem cell transplantation–an evolving treatment for severe autoimmune and inflammatory diseases in rheumatology, neurology and gastroenterology.

Hematology. 2007 Jun;12(3):179-91

Authors: Kapoor S, Wilson AG, Sharrack B, Lobo A, Akil M, Sun L, Dalley CD, Snowden JA

The concept of haemopoietic stem cell transplantation (HSCT) to treat severe autoimmune diseases has been around for several decades. Advances in the safety of HSCT have made it a clinical reality since 1995. Databases have registered around a thousand patients treated specifically for a wide range of diseases, predominantly multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Phase I/II prospective and retrospective studies have supported the potential of autologous HSCT as a treatment option in severely affected patients, with profound and prolonged clinical responses in some diseases, although procedures are generally not curative. Allogeneic HSCT appears to offer curative potential, but the potential of high toxicity has limited its use in this context. The exact role of HSCT remains to be defined, particularly in the context of other advances in the treatment of autoimmune disease. Along with other groups, the European Group for Blood and Marrow Transplantation (EBMT) are overseeing several phase III trials in autologous transplantation. Given the risks of the HSCT, eligibility is restricted to patients who have severe, treatment resistant disease, in whom the prognosis is otherwise poor. This review aims to summarise the current published data in this evolving treatment for relatively rare patients with resistant or rapidly progressive disease where treatment options are otherwise limited. This cross-fertilization of knowledge between many specialties may provide increasing therapeutic opportunities in otherwise untreatable diseases. Moreover, destroying and rebuilding immune systems may provide insights into autoimmune diseases.

PMID: 17558693 [PubMed – indexed for MEDLINE]

 
The use of stem cells for the treatment of autoimmune diseases.

Braz J Med Biol Res. 2007 Dec;40(12):1579-97

Authors: Rosa SB, Voltarelli JC, Chies JA, Pranke P

Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplantation in such diseases aims to destroy the self-reacting immune cells and produce a new functional immune system, as well as substitute cells for tissue damaged in the course of the disease. Significant results, such as the reestablishment of tolerance and a decrease in the recurrence of autoimmune disease, have been reported following stem cell transplantation in patients with autoimmune disease in Brazil and throughout the world. These results suggest that stem cell transplantation has the potential to become an important therapeutic approach to the treatment of various autoimmune diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, Crohn’s disease, autoimmune blood cytopenias, and type I diabetes mellitus.

PMID: 17713674 [PubMed – indexed for MEDLINE]

 
Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes.

Diabetes Metab. 2009 Apr;35(2):85-93. Epub 2009 Feb 20.

Vija L, Farge D, Gautier JF, Vexiau P, Dumitrache C, Bourgarit A, Verrecchia F, Larghero J.

Source

Inserm U697, Paris, France.

Abstract

Mesenchymal stem cells (MSCs) are multipotent non-haematopoietic progenitor cells that are being explored as a promising new treatment for tissue regeneration. Although their immunomodulatory properties are not yet completely understood, their low immunogenic potential together with their effects on immune response make them a promising therapeutic tool for severe refractory autoimmune diseases. Type 1 diabetes is characterized by T cell-mediated autoimmune destruction of pancreatic beta cells. While insulin replacement represents the current therapy for type 1 diabetes, its metabolic control remains difficult, as exogenous insulin cannot exactly mimic the physiology of insulin secretion. Pancreatic or islet transplantation can provide exogenous insulin independence, but is limited by its intrinsic complications and the scarcity of organ donors. In this context, stem cell therapy, based on the generation of insulin-producing cells (IPCs) derived from MSCs, represents an attractive possibility. In this review, we provide a brief characterization of MSC immunomodulatory effects, and present the current experimental evidence for the potential therapeutic efficacy of MSC transplantation in diabetes.

PMID:19230736 [PubMed – indexed for MEDLINE]

 

Cell therapy for autoimmune diseases.

Arthritis Res Ther. 2007;9(2):206

Authors: Dazzi F, van Laar JM, Cope A, Tyndall A

Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases.

PMID: 17367542 [PubMed – indexed for MEDLINE]

 
Targeting improves MSC treatment of inflammatory bowel disease.

Mol Ther. 2010 Jul;18(7):1365-72. Epub 2010 Apr 13.

Targeting improves MSC treatment of inflammatory bowel disease.

Ko IK, Kim BG, Awadallah A, Mikulan J, Lin P, Letterio JJ, Dennis JE.
Department of Orthopedics, Case Western Reserve University, Cleveland, Ohio, USA.
Abstract

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is an inflammatory autoimmune disease characterized by T-cell infiltration to the colon. Mesenchymal stem cells (MSCs) have the potential to rescue IBD owing to their immunosuppressive capabilities and clinical studies have shown positive influence on intestinal graft versus host disease. We demonstrate here a new method to coat MSCs with antibodies against addressins to enhance their delivery to the colon and thereby increase the therapeutic effectiveness. Bioluminescence imaging (BLI) demonstrated that vascular cell adhesion molecule antibody (Ab)-coated MSCs (Ab(VCAM-1)- MSCs) had the highest delivery efficiency to inflamed mesenteric lymph node (MLN) and colon compared to untreated MSCs, Ab(isotype)-MSCs, and Ab(MAdCAM)-MSCs. Therapeutically, when mice with IBD were injected with addressin Ab-coated MSCs, they showed dramatically improved survival rates, higher IBD therapeutic scores, and significantly improved body weight gain compared to mice injected with MSCs only, isotype Ab, free Ab plus MSCs, or vehicle-only controls. These data demonstrate that anti-addressin Ab coating on MSC increased cell delivery to inflamed colon and increased the efficacy of MSC treatment of IBD. This is the first study showing an increased therapeutic efficacy when stem cells are first coated with antibodies specifically target them to inflamed sites.

 
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