Nine Patients with Crohn’s Disease Treated by Intravenous Administration of Mesenchymal Stem Cells

Marjolijn et al. Gut 59:1662

Mesenchymal stem cells are known to be suppressive to immune cells such as T cells, dendritic cells, and natural killer cells. Studies have demonstrated that patients suffering from the immune disease graft versus host enter remission after administration of donor or third party mesenchymal stem cells. One of the manifestations of graft versus host disease is inflammation of the colon, resembling autoimmune colitis and Crohn’s disease.

Some of the previous studies investigating this condition have demonstrated therapeutic effects of mesenchymal stem cells on colonic inflammation. Given this rationale, a recent paper examined the effects of autologous mesenchymal stem cells in the treatment of Crohn’s disease refractory to steroids, immune suppressants, and biologics.

50-100 ml of bone marrow cells were isolated from family members or third-party donors and expanded in vitro. Cells where grown to administer two doses, a week a part, of 1-2 x 10(6) cells per kg body weight. Patients were treated by intravenous administration and followed up for 6 months.

MSC infusion was without side effects, besides a mild allergic reaction probably due to the cryopreservant DMSO in one patient. Baseline median CDAI was 326 (224-378). Three patients showed clinical response (CDAI decrease ≥70 from baseline) 6 weeks post-treatment. Additionally, 3 other patient required surgery, presumably as a result of disease progression.

These data demonstrate that intravenous administration of bone marrow mesenchymal stem cells appears to be safe for treatment of Crohn’s disease, however larger studies are necessary to determine whether statistically significant efficacy exists.

Stem cell therapy shows early promise: Celgene

Crohn’s disease is a favorite amongst mesenchymal stem cell
development companies. This may be because on the one hand, this type of stem
cell possesses anti-inflammatory properties, and on the other hand it has the
potential to regenerate injured tissue. Additionally since the quality of life
of patients with advanced Crohn’s Disease is so poor, and current treatments are
generally ineffective at addressing the root cause, that new treatments usually
receive much support from regulatory agencies. Crohn’s disease is characterized
as a chronic inflammatory condition of the gastrointestinal tract. It is
believed to affects almost one million people in the United States.

Today Celgene announced Phase I safety data on its
placental mesenchymal stem cell product PDA-001 in a trial of 12 patients. The
patients suffered from active moderate-to-severe Crohn’s and were unresponsive
to at least one prior conventional therapy. The treatment with stem cells
comprised two infusions of PDA-001 one week apart. The patients were divided
into 2 groups with 6 patients being administered a lower number of cells and six
a higher number.

According to Celgene, "The study met its primary safety
goal and demonstrated encouraging signs of clinical benefit, including clinical
remission among four patients in the low dose group". Interestingly the company
declined to speculate on why the lower number of cells elicited superior
benefit. As an interesting aside, the company Osiris Therapeutic conducted a
similar clinical trial in Crohn’s Disease using stem cells derived not from
placenta but from bone marrow sources.

The CEO of Celgene’s Cellular Therapeutics unit, Dr. Robert
Hariri stated "We are encouraged that in these patients with Crohn’s disease our
unique, placenta-derived therapies show signs of clinical benefit," he continued
"We will continue to aggressively pursue the clinical development of this and
other cellular therapies derived from what we see as one of the richest sources
of uniquely functional and versatile cells."

The company anticipates moving into Phase II clinical
trials not only in the area of Crohn’s but also in other degenerative
indications.

It is an interesting point that the cells were administered
intravenously. There are some groups that believe stem cells only work if
administered locally. This study suggests that the need for local injection may
not be as important as some others believe. Additionally, since companies like
Cellmedicine use various mesenchymal stem cell sources, the current results
provide US-based scientific evidence supporting at least the rationale for this
approach.