About Crohn’s Disease
- Are there stem cell therapies available for Crohn's disease?
- How close are we? What do we know about Crohn's disease?
- What research is underway?
- Further reading on Crohn's
Are there stem cell therapies available for Crohn’s disease?
Currently, there are no Health Canada or U.S. Food and Drug Administration approved stem cell therapies for treating Crohn’s. Patients researching their options may come across companies with Web sites that say otherwise and offer fee-based stem cell treatments. Many of these claims are not supported by sound scientific evidence and patients are encouraged to review some of the links below before making crucial decisions about their treatment plan.
For the latest developments read our blog entries here.
For more about stem cell clinical trials for Crohn’s disease click here. (For printed version: http://1.usa.gov/1AZVvVa)
How close are we? What do we know about Crohn’s disease?
- Crohn’s is a chronic inflammatory bowel disease that can attack the entire digestive tract, but most commonly affects specific parts of the gut: the lower small intestine, the large intestine, and where the two connect.
- The relapsing and remitting nature of Crohn’s is due to bouts of inflammation that eat away at the digestive tract.
- Although the exact causes remain a mystery, researchers agree that Crohn’s is a multidimensional disease involving an autoimmune component, genetic susceptibility, immune deficiency, and environmental triggers.
- Crohn’s typically strikes people in their teens and 20s or later in their 50s and 60s.
- Crohn’s symptoms overlap with other gastrointestinal disorders, making it difficult to diagnose. It often causes diarrhea and abdominal pain. As the disease worsens, the lining of the digesting tract may be destroyed, resulting abnormal connections (fistulas) or even blockages. Eventually, surgery may be needed to remove damaged parts of intestine, and over time patients may be left with very little of their gut intact.
- Therapies to control Crohn’s include anti-inflammatory drugs and immunological therapies. Currently, there is no cure for this disease.
How can stem cells play a part?
Stem cells may be able to help repair some of the damage caused by inflammation by ‘resetting’ the immune system – making new cells, inhibiting inflammation, stimulating tissue repair and dampening the immune response.
Are there lots of groups working on developing a stem cell therapy?
Many research teams around the globe are working on stem cell therapies for Crohn’s. They are trying to identify the mechanisms that show how stem cells work, which stem cells are the most anti-inflammatory and stimulate the most tissue repair, and how best to safely administer stem cells.
The stem cells being used for transplant studies can be autologous, meaning from the patient, or allogeneic, from a donor. Researchers may manipulate the harvested stem cells before transplanting them. Autologous cells don’t cause graft rejection and don’t require anti-rejection medication. However, not all patients are good candidates for autologous grafts: if a genetic component is at play, transplanting his or her own cells might result in the same inflammatory condition. In those situations, using allogeneic stem cells is better, especially if the donor could be screened to rule out a family history of Crohn’s.
Stem cell research on Crohn’s is moving down a number of different avenues and some successes along the way have yielded early Phase 1/2 clinical trials using mesenchymal stem/stromal cells or adipose (fat) derived stem cells, hematopoietic stem cells from bone marrow or blood, or stem cells from the placenta.
What research is underway?
Before basic stem cell research can be translated into the clinic for patients, it must first be rigorously tested and validated. This involves validating stem cell therapies in animal models of inflammation first and then translating these discoveries to the clinical setting.
The main types of stem cells being investigated for Crohn’s are mesenchymal stem/stromal cells, adipose tissue derived stem cells, and hematopoietic stem cells. Although pre-clinical research is progressing well, questions remain, such as: Can we demonstrate that these stem cells can work in major trials involving many patients? Do we understand the mechanisms that underpin how stem cells work? What way and dose is best to administer the stem cells, and do they need to be given in combination with anti-rejection drugs?
Answering these questions will take time, but the wealth of information generated from labs around the globe is converging to help with the transition from basic research to the clinic. The results are promising and in time may point to a viable stem cell therapy for Crohn’s that can reset the immune system and repair damaged tissue.
Current research using mesenchymal stem/stromal cells
Mesenchymal stem/stromal cells (MSCs) are easily collected from bone marrow, fat and umbilical cord and can be grown into a variety of different cell types. MSCs are promising because they have been shown in pre-clinical studies to dampen the immune system response, inhibit inflammation, stimulate blood vessel formation, repair tissue and help stem cells to engraft. And graft rejection rarely occurs with MSCs, even when donor and recipient are unrelated.
Trials using autologous (from the patient) bone marrow MSCs first showed that MSC therapy could benefit Crohn’s patients. The patients in these trials had active disease that did not respond to any of the current therapies. Enough patients reported an improvement in their symptoms that subsequent trials were launched to more fully explore using MSCs from bone marrow and to test if the same effects could be achieved using MSCs from more readily available sources, such as adipose (fat) tissue.
Current research using adipose (fat) derived stem cells
Adipose (fat) tissue derived stem cells (ASCs) have two qualities that make them a promising candidate for treating Crohn’s: they are regenerative and anti-inflammatory. ASCs make a variety of different cell types (fat, bone, cartilage, muscle, epithelial) and also promote the formation of new blood vessels.
Patients with various types of fistula (abnormal connections between the intestinal tract and adjacent tissues and organs) took part in the first clinical trial that proved that ASCs could work in treating Crohn’s. They experienced no adverse effects and no rejection of cells. Eight weeks after autologous (from the patient) ASCs were injected into the fistulas, they closed in six of eight patients and partially closed in two patients. This success and other early trials paved the way for researchers to launch additional studies exploring the role of ASCs to treat fistulas in Crohn’s and other diseases. The outcome has been so positive that Europe and the United States have granted approval under orphan drug status regulations to market ASCs for treating fistulas.
Researchers are launching studies with more patients and delving deeper into treating Crohn‘s with ASCs. Long-term follow-up studies are assessing the longevity of ASC therapy to provide complete healing of fistulas and prevent their recurrence. At the same time researchers are studying how ASCs work to promote healing – by suppressing inflammation, making new epithelial cells, or both.
Current research using hematopoietic stem cells
A bit of luck led to using hematopoietic stem cells to treat Crohn’s disease: scientists found that leukemia patients with Crohn’s got better after being treated with donor (allogeneic) bone marrow transplants. In recent years very small clinical trials have started to evaluate the use of patient-derived (autologous) hematopoietic stem cell transplants and some are exploring different approaches for mobilizing the stem cells to locations such as peripheral blood, where they are more easily collected than from bone marrow.
Early stage clinical trials are testing whether the allogeneic stem cell approach could help patients with severe, therapy-resistant Crohn’s. Researchers are making great efforts to minimize the chances of graft-versus-host disease by using matched siblings as donors, removing dangerous immune cells (T cells) from the donor graft, and not destroying the patient’s bone marrow completely prior to the transplant. Taken together, this procedure is called a mini-transplant and the intended goal is to increase survival and remission of symptoms.
Further reading on Crohn’s
Readers may wish to peruse the recommended sites and below for more information about Crohn’s and the possible future applications of stem cells to treat this disease.