Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis

Intra-Bone Marrow Administration of Mesenchymal Stem/Stromal Cells Is a Promising Approach for Treating Osteoporosis

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis

A novel therapeutic strategy for esophageal varices using endoscopic treatment combined with splenic artery embolization according to the Child-Pugh classification.

Variceal hemorrhage may cause high rebleeding and mortality rates. Preventing the first episode of variceal bleeding is mandatory in patients with high-risk esophageal varices (EV). This study aimed to identify factors that predict the recurrence of EV after endoscopic treatment (ET), and to develop a reasonable therapeutic strategy for EV in cirrhosis. From January 2012 to December 2014, 45 patients with cirrhosis and high-risk EV underwent ET, including sclerotherapy and/or ligation. Statistical analyses identified factors associated with the recurrence of EV after ET, and the Kaplan-Meier method determined the cumulative variceal recurrence rates. The 1-, 2-, and 3-year cumulative posttreatment recurrence rates for EV were 13.3%, 29.5%, and 32.2%, respectively. No significant differences were evident between the patients with and without variceal recurrences at 1-year posttreatment. The multivariate regression analyses identified a history of partial splenic embolization (PSE) and the pretreatment Child-Pugh classification as independent predictors of variceal recurrences at 2 years (p < 0.05) and 3 years (p < 0.05) posttreatment. While EV did not recur after ET and splenic artery embolization in cases with Child-Pugh class A, the overall posttreatment variceal recurrence rates were 0% and 66.7% when PSE was performed before and after ET, respectively, in those with Child-Pugh class B or C. Splenic artery embolization significantly reduced the hepatic venous pressure gradient and markedly lowered the Child-Pugh score in 15 patients. Adjunctive PSE and pretreatment Child-Pugh class A could be independently associated with reduced cumulative recurrence rates of EV post-ET. From the perspectives of portal hemodynamics and hepatic function, splenic artery embolization before or after ET could prevent posttreatment variceal recurrence in patients with Child-Pugh class A, and PSE before ET could achieve the long-term eradication of EV following ET in those with Child-Pugh class B or C

術前化学療法後にFDG異常集積を認めた縦隔原発非セミノーマ性巨大胚細胞性腫瘍の一切除例

A 32-year-old man presented with a mediastinal non-seminomatous germ cell tumor showing　fluorodeoxyglucose (FDG) accumulation (maximum standardized uptake value = 22.21) and extremely elevated blood α-fetoprotein (AFP) level (9203.0 ng/ml). The patient underwent 4 cycles of neoadjuvant chemotherapy (cisplatin, bleomycin, and etoposide), which normalized the AFP level and reduced the tumor size, allowing complete resection without a support of extracorporeal circulation. Despite preoperative positron emission tomography revealing increased FDG uptake in the residual tumor (maximum standardized uptake value = 3.59), the pathologic evaluation revealed that no viable germ cell tumor cells remained. We believe FDG uptake should not be used as a criterion for surgical resection after neoadjuvant chemotherapy. It is appropriate to resect the residual tumor regardless of FDG uptake after induction chemotherapy if a tumor is resectable and the AFP level normalizes.症例は32歳男性。縦隔原発の非セミノーマ性胚細胞性腫瘍の診断で、PET-CTでFDG異常集積(SUVmax 22.21)、血液検査でAFP の異常高値(9203 ng/ml)を認めた。術前化学療法(シスプラチン、ブレオマイシン、エトポシド)4 サイクル施行後にAFPの正常化と腫瘍の縮小を認め、体外循環を使用することなく完全切除可能であった。術前のPET-CTで残存腫瘍にFDG異常集積(SUVmax 3.59)を依然認めていたにも関わらず、術後の病理診断では生存している悪性細胞を認めなかった。術前化学療法後に外科的切除を行うかどうかの判断基準の一つに、FDG異常集積を用いるべきではない。導入化学療法後に、腫瘍が切除可能でAFPの値が正常化していれば、FDGの集積とは関係なく、残存病変を切除することが望ましいと考えられる

Successful Resection of a Giant Mediastinal Non- Seminomatous Germ Cell Tumor Showing Fluorodeoxyglucose Accumulation after Neoadjuvant Chemotherapy : Report of a Case

A 32-year-old man presented with a mediastinal non-seminomatous germ cell tumor showing　fluorodeoxyglucose (FDG) accumulation (maximum standardized uptake value = 22.21) and extremely elevated blood α-fetoprotein (AFP) level (9203.0 ng/ml). The patient underwent 4 cycles of neoadjuvant chemotherapy (cisplatin, bleomycin, and etoposide), which normalized the AFP level and reduced the tumor size, allowing complete resection without a support of extracorporeal circulation. Despite preoperative positron emission tomography revealing increased FDG uptake in the residual tumor (maximum standardized uptake value = 3.59), the pathologic evaluation revealed that no viable germ cell tumor cells remained. We believe FDG uptake should not be used as a criterion for surgical resection after neoadjuvant chemotherapy. It is appropriate to resect the residual tumor regardless of FDG uptake after induction chemotherapy if a tumor is resectable and the AFP level normalizes.症例は32歳男性。縦隔原発の非セミノーマ性胚細胞性腫瘍の診断で、PET-CTでFDG異常集積(SUVmax 22.21)、血液検査でAFP の異常高値(9203 ng/ml)を認めた。術前化学療法(シスプラチン、ブレオマイシン、エトポシド)4 サイクル施行後にAFPの正常化と腫瘍の縮小を認め、体外循環を使用することなく完全切除可能であった。術前のPET-CTで残存腫瘍にFDG異常集積(SUVmax 3.59)を依然認めていたにも関わらず、術後の病理診断では生存している悪性細胞を認めなかった。術前化学療法後に外科的切除を行うかどうかの判断基準の一つに、FDG異常集積を用いるべきではない。導入化学療法後に、腫瘍が切除可能でAFPの値が正常化していれば、FDGの集積とは関係なく、残存病変を切除することが望ましいと考えられる