Mobilization of multilineage-differentiating stress-enduring cells into the peripheral blood in liver surgery

Abstract

Purpose This study investigated whether liver damage severity relates to the mobilization of multilineage-differentiating stress-enduring (Muse) cells, which are endogenous reparative pluripotent stem cells, into the peripheral blood (PB) and whether the degree of mobilization relates to the recovery of liver volume following human liver surgery. Methods Forty-seven patients who underwent liver surgery were included in the present study. PB-Muse cells were counted before surgery, on postoperative days (PODs) 3 and on POD 7. Liver volume was measured using computed tomography before and after surgery. Results The PB-Muse cell count increased after surgery. The number of PB-Muse cells before surgery was higher, but without statistical significance in the group with neoplasms than in the healthy group that included liver donors (p = 0.065). Forty-seven patients who underwent liver surgery were divided into major hepatic resection (MHR; hepatectomy of three or more segments according to the Couinaud classification, n = 22) and minor hepatic resection (mhr; hepatectomy of two segments or less according to the Couinaud classification, n = 25) groups. PB-Muse cells increased at high rates among MHR patients (p = 0.033). Except for complication cases, PB-Muse cells increased at higher rates in the group with advanced liver volume recovery (p = 0.043). The predictive impact of the rate of increase in PB-Muse cells on the recovery of liver volume was demonstrated by multivariate analysis (OR 11.0, p = 0.014). Conclusions PB-Muse cell mobilization correlated with the volume of liver resection, suggesting that the PB-Muse cell number reflects the degree of liver injury. Given that the degree of PB-Muse cell mobilization was related to liver volume recovery, PB-Muse cells were suggested to contribute to liver regeneration, although this mechanism remains unclear.

Multilineage-Differentiating Stress-Enduring Cells: A Powerful Tool for Tissue Damage Repair

“…The most common sources of Muse cells are bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs). The primary source of Muse cells of peripheral blood origin is thought to be the bone marrow, and given that Muse cells in the peripheral blood enter the tissues from the circulatory system, they are first naturally localized to connective tissues and are thought to be continuously mobilized from the bone marrow to the peripheral blood, where they are then supplied to each organ via the bloodstream [21,29]. Once in the organ, they are sparsely distributed throughout the connective tissues of the organ, such as the dermis, liver, spleen, pancreas, trachea, adipose tissue, dental pulp, and synovial tissue [15,19,26,[30][31][32][33][34], so that Muse cells are spread throughout the different mesenchymal tissues.…”

“…To date, Muse cells have been used in neurological diseases [63,66,[107][108][109][110][111][112], cardiac systemic diseases [39,49,55,75,[113][114][115][116], renal diseases [40,99,117], dermatological diseases [44,78,[118][119][120], liver diseases [29,41,67,101,121], and other diseases to demonstrate their desirable effects in treating and repairing damaged tissues. In these disease models, Muse cells can migrate to the lesion site and spontaneously differentiate into histocompatible cells such as neurons (ectoderm) [43,111,122], cardiomyocytes (mesoderm) [115,123], glomerulocytes (mesoderm) [40,117], vascular endothelial cells (mesoderm) [34,120]and hepatocytes (entoderm) [41,101,121].…”

Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment

“…The dynamics of Muse cells in the peripheral blood of patients with ischemic stroke, AMI, and liver surgery indicate that (1) the peripheral blood-Muse cell number increases following an increase in serum S1P, (2) Muse cells exhibit 3 patterns of change after onset: increase, decrease, and no change, and (3) patients with a higher peripheral blood-Muse cell number show better recovery. 8 , 20 , 21 In an AMI study, patients with a higher number of peripheral blood-Muse cells in the acute phase (by day 7 after onset) exhibited statistically meaningful recovery of cardiac function with a lower occurrence of heart failure in the chronic stage (6 months after onset) compared to patients with no increase in the number of peripheral blood-Muse cells during the acute phase, suggesting the involvement of Muse cells in the innate reparative function. 8 …”

Multilineage-differentiating stress-enduring cells: a powerful tool for tissue damage repair

“…The most common sources of Muse cells are BM-derived MSCs (BM-MSCs) and UC-derived MSCs (UC-MSCs). The primary source of Muse cells of peripheral blood origin is thought to be the bone marrow, and given that Muse cells in the peripheral blood enter the tissues from the circulatory system, they are first naturally localized to connective tissues and are thought to be continuously mobilized from the bone marrow to the peripheral blood, where they are then supplied to each organ via the bloodstream ( Sato et al, 2020 ; Kikuchi et al, 2022 ). Once in the organ, they are sparsely distributed throughout the connective tissues of the organ, such as the dermis, liver, spleen, pancreas, trachea, adipose tissue, dental pulp, and synovial tissue ( Heneidi et al, 2013 ; Tsuchiyama et al, 2013 ; Kinoshita et al, 2015 ; Dezawa, 2016 ; Gimeno et al, 2017 ; Tian et al, 2017 ; Toyoda et al, 2019 ; Aprile et al, 2021 ), so that Muse cells are spread throughout the different mesenchymal tissues.…”

“…To date, Muse cells have been used in neurological diseases ( Uchida H. et al, 2017 ; Shimamura et al, 2017 ; Hori et al, 2020 ; Ozuru et al, 2020 ; Chen et al, 2021 ; Kajitani et al, 2021 ; Suzuki et al, 2021 ; Yin et al, 2023 ), cardiac systemic diseases ( Amin et al, 2018 ; Minatoguchi et al, 2018 ; Tanaka et al, 2018 ; Yamada et al, 2018 ; Yamada et al, 2022 ; Yamada et al, 2022 ; Castillo et al, 2023 ; Wu et al, 2023 ), renal diseases ( Batchelder et al, 2009 ; Uchida N. et al, 2017 ; Uchida et al, 2018 ), dermatological diseases ( Yamauchi et al, 2017 ; Yamauchi, 2018 ; Guo et al, 2020 ; Fei et al, 2021 ; Fujita et al, 2021 ; Fujita et al, 2021 ), liver diseases ( Iseki et al, 2017 ; Nishizuka, 2018 ; Hessheimer et al, 2021b ; Shono et al, 2021 ; Kikuchi et al, 2022 ), and other diseases to demonstrate their desirable effects in treating and repairing damaged tissues. In these disease models, Muse cells can migrate to the lesion site and spontaneously differentiate into histocompatible cells such as neurons (ectoderm) ( Zheng et al, 2018 ; Hori et al, 2020 ; Yamashita et al, 2021 ), cardiomyocytes (mesoderm) ( Noda et al, 2020 ; Yamada et al, 2022 ), glomerulocytes (mesoderm) ( Batchelder et al, 2009 ; Uchida N. et al, 2017 ), vascular endothelial cells (mesoderm) ( Kinoshita et al, 2015 ; Yamauchi, 2018 ) and hepatocytes (entoderm) ( Iseki et al, 2017 ; Hessheimer et al, 2021b ; Shono et al, 2021 ).…”