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Vol. 153. Issue 9.
Pages 341-346 (November 2019)
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Vol. 153. Issue 9.
Pages 341-346 (November 2019)
Original article
DOI: 10.1016/j.medcle.2019.01.034
Effectiveness of umbilical cord mesenchymal stem cells in patients with critical limb ischemia
Efectividad de las células madre mesenquimales del cordón umbilical en pacientes con isquemia crítica de extremidades
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Wen-Hui Gaoa,, Hong-Ye Gaoa,, Yue-Tong Lib, Ping-Ping Huanga,
Corresponding author
huangpp@ihcams.ac.cn

Corresponding author.
a Institute of Hematology, General Medical Center, Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
b Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Table 1. Patient characteristics.
Table 2. Distribution of T-lymphocyte subsets (mean±SE) in CLI patients.
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Abstract
Introduction and objective

Transplantation of umbilical cord mesenchymal stem cells (UC-MSCs) has been shown to be effective in treating critical limb ischemia (CLI). However, the mechanism of MSCs-mediated improvements, especially on the immune-inflammatory aspects of this disease, is still unknown. In this study, we investigated the changes in T-lymphocyte subpopulations and inflammatory mediators (such as IL-6, IL-10 and TNF-α) in PBMCs from CLI patients after UC-MSCs treatment and correlation between inflammatory mediators and EPCs.

Patients and methods

8 patients received UC-MSCs transplantation. Before the treatment, at 24h and 1 month thereafter, peripheral blood samples were collected from 8 patients and 8 healthy volunteers. Patients were evaluated for changes in IL-6, IL-10, TNF-α and levels of circulating EPCs.

Results

TNF-α and IL-6 serum levels increased at 24h (p=0.017, p=0.099) after treatment and then decreased at 1 month (p=0.031, p=0.072) compared with those before treatment. The percentages of CD3+T, CD3+CD4+T-lymphocytes and NK cells decreased significantly after UC-MSCs treatment (p=0.002, p=0.012 and p=0.029, respectively). TNF-α (r=−0.602, p=0.038) was shown to be inversely correlated with the number of circulating EPCs.

Conclusions

This study demonstrates that UC-MSCs have anti-inflammatory and immunomodulation properties in CLI and suggests that UC-MSCs promote healing of non-healing wounds.

Keywords:
Critical limb ischemia
Peripheral arterial disease
Umbilical cord
Mesenchymal stem cell
Immunomodulatory
Resumen
Introducción y objetivo

El trasplante de células madre mesenquimales del cordón umbilical (CMM-CU) ha demostrado eficacia en el tratamiento de la isquemia crítica de las extremidades (ICE). Sin embargo, se desconoce el mecanismo de las mejoras mediadas por las CMM, especialmente en los aspectos inmune-inflamatorios de esta enfermedad. Este estudio analiza los cambios en las subpoblaciones de linfocitos T y en los mediadores inflamatorios (como IL-6, IL-10 y TNF-α) en CMSP de pacientes con ICE después del tratamiento con CMM-CU y estudia la correlación entre mediadores inflamatorios y células progenitoras endoteliales (CPE).

Pacientes y métodos

Ocho pacientes recibieron trasplante de CMM-CU. Se recogieron muestras de sangre periférica de 8 pacientes y 8 voluntarios sanos, antes del tratamiento, a las 24h y un mes después. Los pacientes fueron evaluados para detectar cambios en IL-6, IL-10, TNF-α y niveles de CPE circulantes.

Resultados

Los niveles séricos de TNF-α e IL-6 aumentaron 24h después del tratamiento (p=0,017, p=0,099) y luego disminuyeron al mes (p=0,031, p=0,072) en comparación con los niveles antes del tratamiento. Los porcentajes de CD3+T, CD3+CD4+ linfocitos T y células NK disminuyeron significativamente después del tratamiento con CMM-CU (p=0,002, p=0,012 y p=0,029, respectivamente). TNF-α (r=−0,602, p=0,038) demostró estar correlacionada inversamente con el número de CPE circulantes.

Conclusiones

Este estudio demuestra que las CMM-CU tienen propiedades antiinflamatorias e inmunomoduladoras en la ICE y sugieren que las CMM-CU promueven la curación de heridas que no cicatrizan.

Palabras clave:
Isquemia crítica de extremidades
Enfermedad arterial periférica
Cordón umbilical
Células madre mesenquimatosas
Inmunomodulador

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