Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning

Choi, Da Won; Cho, Kyung‐Ah; Lee, Hyun‐Ji; Kim, Yu‐Hee; Woo, Kyong‐Je; Park, Joowon; Ryu, Kyung‐Ha; Woo, So Youn

doi:10.3892/ijmm.2020.4657

Cited by 12 publications

(14 citation statements)

References 38 publications

(48 reference statements)

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“…We previously confirmed that human palatine tonsil-derived mesenchymal stem cells (T-MSCs) effectively recovered body weight in a chemotherapy-preconditioned bone marrow transplantation (BMT) mouse model [13,14]. A similar effect was observed when we used either T-MSCs or a conditioned medium from T-MSCs.…”

Section: Introductionsupporting

confidence: 53%

Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Cho

Choi

Kim

et al. 2021

Cells

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Skeletal muscle mass is decreased under a wide range of pathologic conditions. In particular, chemotherapy is well known for inducing muscle loss and atrophy. Previous studies using tonsil-derived mesenchymal stem cells (T-MSCs) or a T-MSC-conditioned medium showed effective recovery of total body weight in the chemotherapy-preconditioned bone marrow transplantation mouse model. This study investigated whether extracellular vesicles of T-MSCs, such as exosomes, are a key player in the recovery of body weight and skeletal muscle mass in chemotherapy-treated mice. T-MSC exosomes transplantation significantly decreased loss of total body weight and muscle mass in the busulfan-cyclophosphamide conditioning regimen in BALB/c recipient mice containing elevated serum activin A. Additionally, T-MSC exosomes rescued impaired C2C12 cell differentiation in the presence of activin A in vitro. We found that T-MSC exosomes possess abundant miR-145-5p, which targets activin A receptors, ACVR2A, and ACVR1B. Indeed, T-MSC exosomes rescue muscle atrophy both in vivo and in vitro via miR-145-5p dependent manner. These results suggest that T-MSC exosomes have therapeutic potential to maintain or improve skeletal muscle mass in various activin A elevated pathologic conditions.

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Section: Introductionsupporting

confidence: 53%

Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Cho

Choi

Kim

et al. 2021

Cells

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“…In terms of HSCs, half of the selected studies[ 8 , 10 , 15 , 16 , 18 , 20 - 22 , 25 ] used cells from human umbilical cord blood (UCB), while the other half[ 9 , 11 - 14 , 17 , 18 , 23 , 24 ] used cells from animal BM (Table 1 ). Wu et al [ 20 ] reported the transplantation of the pool of human nucleated cells.…”

Section: Resultsmentioning

confidence: 99%

How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models

Garrigós¹,

Oliveira²,

Nucci³

et al. 2022

WJSC

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BACKGROUND Bone marrow transplantation (BMT) can be applied to both hematopoietic and nonhematopoietic diseases; nonetheless, it still comes with a number of challenges and limitations that contribute to treatment failure. Bearing this in mind, a possible way to increase the success rate of BMT would be cotransplantation of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) to improve the bone marrow niche and secrete molecules that enhance the hematopoietic engraftment. AIM To analyze HSC and MSC characteristics and their interactions through cotransplantation in murine models. METHODS We searched for original articles indexed in PubMed and Scopus during the last decade that used HSC and MSC cotransplantation and in vivo BMT in animal models while evaluating cell engraftment. We excluded in vitro studies or studies that involved graft versus host disease or other hematological diseases and publications in languages other than English. In PubMed, we initially identified 555 articles and after selection, only 12 were chosen. In Scopus, 2010 were identified, and six were left after the screening and eligibility process. RESULTS Of the 2565 articles found in the databases, only 18 original studies met the eligibility criteria. HSC distribution by source showed similar ratios, with human umbilical cord blood or animal bone marrow being administered mainly with a dose of 1 × 10 7 cells by intravenous or intrabone routes. However, MSCs had a high prevalence of human donors with a variety of sources (umbilical cord blood, bone marrow, tonsil, adipose tissue or fetal lung), using a lower dose, mainly 10 6 cells and ranging 10 4 to 1.5 × 10 7 cells, utilizing the same routes. MSCs were characterized prior to administration in almost every experiment. The recipient used was mostly immunodeficient mice submitted to low-dose irradiation or chemotherapy. The main technique of engraftment for HSC and MSC cotransplantation evaluation was chimerism, followed by hematopoietic reconstitution and survival analysis. Besides the engraftment, homing and cellularity were also evaluated in some studies. CONCLUSION The preclinical findings validate the potential of MSCs to enable HSC engraftment in vivo in both xenogeneic and allogeneic hematopoietic cell transplantation animal models, in the absence of toxicity.

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“…Because TMSCs successfully maintain MSC-specific properties during freezing and thawing, and also up to passage 15 during long-term in vitro cell culture [ 36 ], TMSCs are a good MSC candidate for clinical cell therapy. Our recent studies suggested that co-transplantation of bone marrow cells and TMSCs improved the outcomes of bone marrow transplantation by enhancing bone marrow cell engraftment [ 37 ] and thymus regeneration [ 38 ]. Because the infection is significantly associated with morbidity and mortality among patients receiving allogeneic bone marrow cells, enhancing neutrophil function is critical in maintaining host immune defences against invading microorganisms during bone marrow transplantation.…”

Section: Discussionmentioning

confidence: 99%

Procollagen C-Endopeptidase Enhancer 2 Secreted by Tonsil-Derived Mesenchymal Stem Cells Increases the Oxidative Burst of Promyelocytic HL-60 Cells

Yoon

Cho

Kim

et al. 2022

Biology

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Reactive oxygen species (ROS) generated by neutrophils provide a frontline defence against invading pathogens. We investigated the supportive effect of tonsil-derived mesenchymal stem cells (TMSCs) on ROS generation from neutrophils using promyelocytic HL-60 cells. Methods: Differentiated HL-60 (dHL-60) cells were cocultured with TMSCs isolated from 25 independent donors, and ROS generation in dHL-60 cells was measured using luminescence. RNA sequencing and real-time PCR were performed to identify the candidate genes of TMSCs involved in augmenting the oxidative burst of dHL-60 cells. Transcriptome analysis of TMSCs derived from 25 independent donors revealed high levels of procollagen C-endopeptidase enhancer 2 (PCOLCE2) in TMSCs, which were highly effective in potentiating ROS generation in dHL-60 cells. In addition, PCOLCE2 knockdown in TMSCs abrogated TMSC-induced enhancement of ROS production in dHL-60 cells, indicating that TMSCs increased the oxidative burst in dHL-60 cells via PCOLCE2. Furthermore, the direct addition of recombinant PCOLCE2 protein increased ROS production in dHL-60 cells. These results suggest that PCOLCE2 secreted by TMSCs may be used as a therapeutic candidate to enhance host defences by increasing neutrophil oxidative bursts. PCOLCE2 levels in TMSCs could be used as a marker to select TMSCs exhibiting high efficacy for enhancing neutrophil oxidative bursts.

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Co‑transplantation of tonsil‑derived mesenchymal stromal cells in bone marrow transplantation promotes thymus regeneration and T cell diversity following cytotoxic conditioning

Cited by 12 publications

References 38 publications

Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

Mesenchymal Stem Cell-Derived Exosomes Protect Muscle Loss by miR-145-5p Activity Targeting Activin A Receptors

How mesenchymal stem cell cotransplantation with hematopoietic stem cells can improve engraftment in animal models

Procollagen C-Endopeptidase Enhancer 2 Secreted by Tonsil-Derived Mesenchymal Stem Cells Increases the Oxidative Burst of Promyelocytic HL-60 Cells

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