AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells

Qu, Zhiguo; Guo, Shengnan; Fang, Guojun; Cui, Zhenghong; Liu, Ying

doi:10.1007/s12013-014-0378-6

Cited by 19 publications

(21 citation statements)

References 24 publications

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“…In addition to AKT activation, we also observed increased transcript levels of AKT itself as well as other pathway-associated genes. This finding is consistent with the known interaction between AKT phosphorylation and AKT gene expression [67]. …”

Section: Discussionsupporting

confidence: 92%

Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes

Middleton

Rogers

Couto

et al. 2018

J of Extracellular Vesicle

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Newts can regenerate amputated limbs and cardiac tissue, unlike mammals which lack broad regenerative capacity. Several signaling pathways involved in cell proliferation, differentiation and survival during newt tissue regeneration have been elucidated, however the factors that coordinate signaling between cells, as well as the conservation of these factors in other animals, are not well defined. Here we report that media conditioned by newt limb explant cells (A1 cells) protect mammalian cardiomyocytes from oxidative stress-induced apoptosis. The cytoprotective effect of A1-conditioned media was negated by exposing A1 cells to GW4869, which suppresses the generation of extracellular vesicles (EVs). A1-EVs are similar in diameter (~100–150 nm), structure, and share several membrane surface and cargo proteins with mammalian exosomes. However, isolated A1-EVs contain significantly higher levels of both RNA and protein per particle than mammalian EVs. Additionally, numerous cargo RNAs and proteins are unique to A1-EVs. Of particular note, A1-EVs contain numerous mRNAs encoding nuclear receptors, membrane ligands, as well as transcription factors. Mammalian cardiomyocytes treated with A1-EVs showed increased expression of genes in the PI3K/AKT pathway, a pivotal player in survival signaling. We conclude that newt cells secrete EVs with diverse, distinctive RNA and protein contents. Despite ~300 million years of evolutionary divergence between newts and mammals, newt EVs confer cytoprotective effects on mammalian cardiomyocytes.

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Section: Discussionsupporting

confidence: 92%

Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes

Middleton

Rogers

Couto

et al. 2018

J of Extracellular Vesicle

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“…PLT-related parameters, including platelet count, volume, mean volume and distribution width decreased post-operation compared to pre-operation. Similar results on safety have been reported in our previous study, in which we injected hUC-MSCs into rats and found hUC-MSCs located in the rat non-union area that differentiated into osteoblasts, as well as no local or systematic manifestations of toxic reactions and graft vs. host disease during and after transplantation (11,12). Based on the above results, this approach is relatively safe.…”

Section: Discussionsupporting

confidence: 89%

“…Thus, stem cell transplantation has gradually emerged as a promising approach for the treatment of ONFH (8,16,17). In previous studies, we grafted human UC-derived MSCs (hUC-MSCs) to treat non-union in rats and human (11–13). Our results demonstrated the safety and efficacy of osteoblastic differentiation of hUC-MSCs.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of umbilical cord-derived mesenchymal stem cell-based therapy for osteonecrosis of the femoral head: A three-year follow-up study

Chen

Yin

et al. 2016

Molecular Medicine Reports

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This is a retrospective analysis of the clinical effects of transplant of mesenchymal stem cells (MSCs) derived from human umbilical cord-derived MSCs (hUC-MSCs) for the treatment of osteonecrosis of the femoral head (ONFH). The biological characteristics of hUC-MSCs were assessed using flow cytometry. Nine eligible patients were enrolled in the study as they adhered to the Association Research Circulation Osseous (ARCO) classification of stage II–IIIa, and hUC-MSCs were grafted by intra-arterial infusion. Organize effective perfusion was assessed using the oxygen delivery index (ODI). The results showed that the ODI was increased at three days post-operation. The MRI results revealed that at 12 and 24 months after treatment, the necrotic volume of the femoral heads was significantly reduced. No obvious abnormalities were observed. Taken together, these data indicate that intra-arterially infused hUC-MSCs migrate into the necrotic field of femoral heads and differentiate into osteoblasts, thus improving the necrosis of femoral heads. This finding suggested that intra-arterial infusion of hUC-MSCs MSCs is a feasible and relatively safe method for the treatment of femoral head necrosis.

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“…Fully informed consent was obtained several weeks prior to delivery. HUC-MSC were isolated and propagated as previously described (10–13). UCs were filled with 0.1% collagenase (Sigma-Aldrich, St. Louis, MO, USA) in PBS and incubated at 37°C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, MSCs can be isolated from bone marrow, umbilical cord (UC) blood, and connective tissue (Wharton's jelly) (9), and can be expanded in culture to use as a source of stem cells to elicit cardiac repair. In previous studies, we investigated the safety and efficacy of human UC-MSCs (HUC-MSCs) in rat (10–12) and human bone non-union (13). …”

Section: Introductionmentioning

confidence: 99%

Functional characterization of human umbilical cord-derived mesenchymal stem cells for treatment of systolic heart failure

Fang

Yin²,

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Congestive heart failure (HF) is a leading cause of morbidity and mortality worldwide. Although advances in medical therapy, mechanical support and heart transplantation have been made, almost half of all patients with HF succumb to the disease within five years of the initial diagnosis. Therefore, treatment methods need to be identified to restore the structure and function of cardiac muscle. Three patients with HF caused by ischemic cardiomyopathy received human umbilical cord-derived mesenchymal stem cell (HUC-MSC) intravenous infusion were included in the present study. Two patients demonstrated a 65.1% increase in left ventricular ejection fraction (LVEF) at the end of 3 months, which was maintained increasing 47.8% at the end of 12 months post-HUC-MSC intravenous infusion. LVEF of patient 1 decreased slowly in the observation period. This LVEF improvement was associated with significant improvements in the clinical parameters of the New York Heart Association class, and six-minute walk test in the coupled time. The third patient showed significant improvement in the six-minute walk test at the end of 12 months, while the other parameters did not change obviously. There were no severe adverse events during and post-HUC-MSC transplantation. During follow-up, no other immunosuppressive drugs were used. In conclusion, HUC-MSC therapy is a reasonable salvage treatment in HF. Future large-scale randomized clinical trials are likely to be designed to elucidate the efficacy of the HUC-MSC transplantation therapy on HF.

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AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells

Cited by 19 publications

References 24 publications

Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes

Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes

Efficacy of umbilical cord-derived mesenchymal stem cell-based therapy for osteonecrosis of the femoral head: A three-year follow-up study

Functional characterization of human umbilical cord-derived mesenchymal stem cells for treatment of systolic heart failure

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