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Allogeneic mesenchymal stem cell transplantation in seven patients with refractory inflammatory bowel disease
  1. Jun Liang,
  2. Huayong Zhang,
  3. Dandan Wang,
  4. Xuebing Feng,
  5. Hong Wang,
  6. Bingzhu Hua,
  7. Bujun Liu,
  8. Lingyun Sun
  1. Department of Immunology and Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
  1. Correspondence to Dr Lingyun Sun, Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, Jiangsu 210008, China; lingyunsun2001{at}yahoo.com.cn

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We refer to two articles by Duijvestein et al and Ciccocioppo et al1 2 in which the authors suggest that administration of autologous bone marrow-derived mesenchymal stem cells (MSCs) is safe and feasible in the treatment of refractory Crohn's disease (CD). However, to date there are few data about allogeneic MSC transplantation (MSCT) for patients with inflammatory bowel disease (IBD).

We wish to report our experience of allogeneic MSCT in seven patients with IBD.

Infused allogeneic MSCs were obtained from the bone marrow or umbilical cord. Bone marrow was aspirated from healthy relatives of three patients. Umbilical cords were obtained from local maternity hospitals after normal deliveries. The isolated MSCs were given by intravenous infusions as 1×106 cells per kilogram of body weight.

Four of the included seven patients had CD and three had ulcerative colitis (UC). Table 1 lists the patient demographics and drug regimens received at the time of MSCT. Mean age was 29 years (range 24–41). Mean disease duration was 60.4 months (range 6–120). After MSCT, all patients had a minimum follow-up of 6 months, with a mean follow-up of 19 months (range 6–32). After MSCT, all patients continued their treatment with steroids and/or immunosuppressants as with the therapies before the transplantation. Three patients received a tapering dose of steroids and dosages at the last follow-up ranged from 10 to 12.5 mg. Two patients also tapered the dose of steroids after MSCT, but needed to go back to intravenous steroids because of a relapse. One patient weaned himself off steroids more than 2 years before transplantation, recognising the dangers of continued steroid medication, and never got back to steroids again after MSCT.

Table 1

Characteristics of the seven enrolled patients before and after MSCT

Diarrhoea frequency and abdominal pain/cramps gradually improved in all the seven patients, accompanied by a significant reduction in Crohn's Disease Activity Index scores in CD patients and Clinical Activity Index scores in UC patients. At the 3-month visit, five patients achieved remission and maintenance of remission lasted for more than 24 months in two patients. Two patients had a relapse at 6 and 7 months after MSCT. A significant reduction in fistula size and drainage was found in one patient. Endoscopic improvement was observed by a decrease in Endoscopic Index of Severity score from 19.1 to 4.2 points at 4 months and from 14.5 to 3 points at 3 months in two CD patients, as well as a decrease in Endoscopic Activity Index from 7 to 5 at 5 months in a UC patient (figure 1). Rough mucosa, polypoid lesions and ulcers significantly decreased after MSC infusion. The histological features of biopsy specimens changed apparently in these three patients. After MSCT, the extent of the inflamed area and the dense lymphocytic infiltration in the mucosa propria was reduced.

Figure 1

Endoscopic healing was found in three patients after mesenchymal stem cell transplantation (MSCT). (A, B) From patient 2 at 0 and 4 months after infusion, respectively. (C, D) From patient 3 at 0 and 3 months after infusion, respectively. (E, F) From patient 5 at 0 and 5 months after infusion, respectively (0: at the time of MSCT).

One patient felt hot in the face for no more than 6 hours after MSC infusion. Another patient described insomnia on the first night after infusion. A third patient experienced 2 days of low fever, where the frequency of diarrhoea increased from 6–10 to 12–13 times per day. These symptoms restored quickly without any medical intervention. No other adverse events were observed during or immediately after infusions of MSCs in any of the seven patients with IBD.

In summary, our data show that allogeneic MSCT is safe and may contribute to clinical improvement in patients with refractory CD and UC, although the mechanisms of action underlying the clinical effects of MSCs still need to be clarified. More clinical trials and follow-up periods are warranted to validate our finding.

Acknowledgments

We would like to thank Dr J Snowden (University of Sheffield, UK) and Prof. R Silver (MUSC, USA) for reviewing this manuscript.

References

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Footnotes

  • Funding This study was supported by grants from Jiangsu Province Ke Jiao Xin Wei Program, Jiangsu Province Natural Science Foundation (BK2009034), Nanjing Health Bureau Young Scientists Launching Project (QYK09174) and Jiangsu Province Health Research Program (LW201009).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Affiliated Drum Tower Hospital of Nanjing University Medical School.

  • Provenance and peer review Not commissioned; internally peer reviewed.

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