Safety and therapeutic effect of mesenchymal stem cell infusion on moderate to severe ulcerative colitis

Jianxia Hu, Gang Zhao, Lize Zhang, Cuixia Qiao, Aiping Di, Hong Gao, Hong Xu, Jianxia Hu, Gang Zhao, Lize Zhang, Cuixia Qiao, Aiping Di, Hong Gao, Hong Xu

Abstract

One of the primary targets of the clinical treatment of ulcerative colitis (UC) is to repair the damaged colonic mucosa. Mesenchymal stem cells (MSCs) have therapeutic potential in regenerative medicine due to their differentiation capacity and their secretion of numerous bioactive molecules. The present study describes a clinical trial (trial registration no. NCT01221428) investigating the safety and therapeutic effect of MSCs derived from human umbilical cord on moderate to severe UC. Thirty-four patients with UC were included in group I and treated with MSC infusion in addition to the base treatment, and thirty-six patients were in group II and treated with normal saline in addition to the base treatment. One month after therapy, 30/36 patients in group I showed good response, and diffuse and deep ulcer formation and severe inflammatory mucosa were improved markedly. During the follow up, the median Mayo score and histology score in group I were decreased while IBDQ scores were significantly improved compared with before treatment and group II (P<0.05). Compared with group II, there were no evident adverse reactions after MSC infusion in any of the patients in group I, and no chronic side effects or lingering effects appeared during the follow-up period. In conclusion, MSC infusion might be a useful and safe therapy for treating UC.

Keywords: cell therapy; immune regulation; mesenchymal stem cells; mucosal healing; ulcerative colitis.

Figures

Figure 1.
Figure 1.
Procedure of the trial. UC, ulcerative colitis; MSC, mesenchymal stem cell.
Figure 2.
Figure 2.
Endoscopic findings of patients in group I before and after therapy.
Figure 3.
Figure 3.
Ratio of clinical response and change of Mayo scores over time. (A) The ratio of clinical response (>3 points decrease in Mayo score) in groups I (n=34) and II (n=36). *P=0.007 vs. group II. (B) The change of Mayo scores in groups I and II over time. *P

Figure 4.

Pathological findings and change in…

Figure 4.

Pathological findings and change in histological scores over time. (A) The change of…

Figure 4.
Pathological findings and change in histological scores over time. (A) The change of pathological findings in patients of group I before and after therapy; magnification, ×10. (B) The change of histological scores in the two groups over time. *P

Figure 5.

Change of IBDQ scores over…

Figure 5.

Change of IBDQ scores over time in groups I and II. *P

Figure 5.
Change of IBDQ scores over time in groups I and II. *P

Figure 6.

Change of (A) CRP and…

Figure 6.

Change of (A) CRP and (B) ESR in groups I and II. Three…

Figure 6.
Change of (A) CRP and (B) ESR in groups I and II. Three months after therapy, the levels of CRP and ESR in the two groups significantly decreased at the third month compared with the baseline measurement; *P
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References
    1. Chinnadurai R, Ng S, Velu V, Galipeau J. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease. World J Gastroenterol. 2015;21:4779–4787. doi: 10.3748/wjg.v21.i16.4779. - DOI - PMC - PubMed
    1. Hiraoka S, Kato J, Moritou Y, Takei D, Inokuchi T, Nakarai A, Takahashi S, Harada K, Okada H, Yamamoto K. The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. BMC Gastroenterol. 2015;15:53. doi: 10.1186/s12876-015-0285-3. - DOI - PMC - PubMed
    1. Sameshima S, Koketsu S, Takeshita E, Kubota Y, Okuyama T, Saito K, Ueda Y, Sawada T, Oya M. Surgical resections of ulcerative colitis associated with dysplasia or carcinoma. World J Surg Oncol. 2015;13:70. doi: 10.1186/s12957-015-0499-4. - DOI - PMC - PubMed
    1. Chande N, Tsoulis DJ, MacDonald JK. Azathioprine or 6-mercaptopurine for induction of remission in Crohns disease. Cochrane Database Syst Rev. 2013;30:CD000545. - PubMed
    1. Naganuma M, Fujii T, Watanabe M. Treatment strategy for refractory inflammatory bowel disease to improve endoscopic lesions and long-term prognosis. Nihon Rinsho Meneki Gakkai Kaishi. 2012;35:99–106. doi: 10.2177/jsci.35.99. (In Japanese) - DOI - PubMed
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Figure 4.
Figure 4.
Pathological findings and change in histological scores over time. (A) The change of pathological findings in patients of group I before and after therapy; magnification, ×10. (B) The change of histological scores in the two groups over time. *P

Figure 5.

Change of IBDQ scores over…

Figure 5.

Change of IBDQ scores over time in groups I and II. *P

Figure 5.
Change of IBDQ scores over time in groups I and II. *P

Figure 6.

Change of (A) CRP and…

Figure 6.

Change of (A) CRP and (B) ESR in groups I and II. Three…

Figure 6.
Change of (A) CRP and (B) ESR in groups I and II. Three months after therapy, the levels of CRP and ESR in the two groups significantly decreased at the third month compared with the baseline measurement; *P
Similar articles
Cited by
References
    1. Chinnadurai R, Ng S, Velu V, Galipeau J. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease. World J Gastroenterol. 2015;21:4779–4787. doi: 10.3748/wjg.v21.i16.4779. - DOI - PMC - PubMed
    1. Hiraoka S, Kato J, Moritou Y, Takei D, Inokuchi T, Nakarai A, Takahashi S, Harada K, Okada H, Yamamoto K. The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. BMC Gastroenterol. 2015;15:53. doi: 10.1186/s12876-015-0285-3. - DOI - PMC - PubMed
    1. Sameshima S, Koketsu S, Takeshita E, Kubota Y, Okuyama T, Saito K, Ueda Y, Sawada T, Oya M. Surgical resections of ulcerative colitis associated with dysplasia or carcinoma. World J Surg Oncol. 2015;13:70. doi: 10.1186/s12957-015-0499-4. - DOI - PMC - PubMed
    1. Chande N, Tsoulis DJ, MacDonald JK. Azathioprine or 6-mercaptopurine for induction of remission in Crohns disease. Cochrane Database Syst Rev. 2013;30:CD000545. - PubMed
    1. Naganuma M, Fujii T, Watanabe M. Treatment strategy for refractory inflammatory bowel disease to improve endoscopic lesions and long-term prognosis. Nihon Rinsho Meneki Gakkai Kaishi. 2012;35:99–106. doi: 10.2177/jsci.35.99. (In Japanese) - DOI - PubMed
Show all 46 references
Related information
LinkOut - more resources
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM

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The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

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Figure 5.
Figure 5.
Change of IBDQ scores over time in groups I and II. *P

Figure 6.

Change of (A) CRP and…

Figure 6.

Change of (A) CRP and (B) ESR in groups I and II. Three…

Figure 6.
Change of (A) CRP and (B) ESR in groups I and II. Three months after therapy, the levels of CRP and ESR in the two groups significantly decreased at the third month compared with the baseline measurement; *P
Similar articles
Cited by
References
    1. Chinnadurai R, Ng S, Velu V, Galipeau J. Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease. World J Gastroenterol. 2015;21:4779–4787. doi: 10.3748/wjg.v21.i16.4779. - DOI - PMC - PubMed
    1. Hiraoka S, Kato J, Moritou Y, Takei D, Inokuchi T, Nakarai A, Takahashi S, Harada K, Okada H, Yamamoto K. The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. BMC Gastroenterol. 2015;15:53. doi: 10.1186/s12876-015-0285-3. - DOI - PMC - PubMed
    1. Sameshima S, Koketsu S, Takeshita E, Kubota Y, Okuyama T, Saito K, Ueda Y, Sawada T, Oya M. Surgical resections of ulcerative colitis associated with dysplasia or carcinoma. World J Surg Oncol. 2015;13:70. doi: 10.1186/s12957-015-0499-4. - DOI - PMC - PubMed
    1. Chande N, Tsoulis DJ, MacDonald JK. Azathioprine or 6-mercaptopurine for induction of remission in Crohns disease. Cochrane Database Syst Rev. 2013;30:CD000545. - PubMed
    1. Naganuma M, Fujii T, Watanabe M. Treatment strategy for refractory inflammatory bowel disease to improve endoscopic lesions and long-term prognosis. Nihon Rinsho Meneki Gakkai Kaishi. 2012;35:99–106. doi: 10.2177/jsci.35.99. (In Japanese) - DOI - PubMed
Show all 46 references
Related information
LinkOut - more resources
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 6.
Figure 6.
Change of (A) CRP and (B) ESR in groups I and II. Three months after therapy, the levels of CRP and ESR in the two groups significantly decreased at the third month compared with the baseline measurement; *P

References

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    1. Hiraoka S, Kato J, Moritou Y, Takei D, Inokuchi T, Nakarai A, Takahashi S, Harada K, Okada H, Yamamoto K. The earliest trough concentration predicts the dose of tacrolimus required for remission induction therapy in ulcerative colitis patients. BMC Gastroenterol. 2015;15:53. doi: 10.1186/s12876-015-0285-3.
    1. Sameshima S, Koketsu S, Takeshita E, Kubota Y, Okuyama T, Saito K, Ueda Y, Sawada T, Oya M. Surgical resections of ulcerative colitis associated with dysplasia or carcinoma. World J Surg Oncol. 2015;13:70. doi: 10.1186/s12957-015-0499-4.
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