Chronic neuropathic pain is caused by dysfunction of the peripheral nerves associated with the somatosensory system. Mesenchymal stem cells (MSCs) have attracted attention as promising cell therapeutics for chronic pain; however, their clinical application has been hampered by the poor in vivo survival and low therapeutic efficacy of transplanted cells. Increasing evidence suggests enhanced therapeutic efficacy of spheroids formed by three-dimensional culture of MSCs. In the present study, we established a neuropathic pain murine model by inducing a chronic constriction injury through ligation of the right sciatic nerve and measured the therapeutic effects and survival efficacy of spheroids. Monolayer-cultured and spheroids were transplanted into the gastrocnemius muscle close to the damaged sciatic nerve. Transplantation of spheroids alleviated chronic pain more potently and exhibited prolonged in vivo survival compared to monolayer-cultured cells. Moreover, spheroids significantly reduced macrophage infiltration into the injured tissues. Interestingly, the expression of mouse-origin genes associated with inflammatory responses, Ccl11/Eotaxin, interleukin 1A, tumor necrosis factor B, and tumor necrosis factor, was significantly attenuated by the administration of spheroids compared to that of monolayer. These results suggest that MSC spheroids exhibit enhanced in vivo survival after cell transplantation and reduced the host inflammatory response through the regulation of main chronic inflammatory response-related genes.

Benzotriazol-1-yl akyl carbonate 1 has been found to be a new convenient and inexpensive coupling agent to prepare an active ester 2 for the synthesis of an amide 3 in good yield and with high purity.During the process of o w research for the preparation of a peristaltic stimulant, Cisapride' (3a) wluch contains an amide bond in its structure, we felt the need of more convenient and inexpensive method to prepare an amide bond in more yield and with higher purity than the conventional method.The representative one of conventional methods to form an amide bond is to react a primary or secondary amine with a suitable active este?. This reaction is generally carried out in the same vessel like one reaction from a carboxylic acid through an active ester to an amide which is a goal. 2547 LEE ET AL.The most popular and useful active ester is the one which is easily prepared by reacting a carboxylic acid with 1-HOBT (I-hydroxybenzotriazole) through the intercession of DCC ( NJ" dicyclohexylcarbodiimide)a. But this method has an defect in that DCC used as a coupling agent to prepare an active ester is transformed into DCU (N,N'-dicyclohexylu) atter the reaction preparing an active ester and this DCU is not easily removed but very often remains in a product, an amide which is usually solid'.In order to remove a problem provoked by DCC and prepare an amide economically in good yield, we have developed a new coupling agent, benzotriazol-1-yl alkyl carbonate (BAC) which can afford an active ester derived from 1-HOBT. BAC which is called a new coupling agent by us has been used as an agent carbethoxylating an alcohol, a thiol, and an a~n i n e~~~. According to our search, we have firstly used BAC as a coupling agent to afford an active ester by being treated with a carboxylic acid.On the one hand, in 1983, Mitsuru UEDA, et al, reported6 that 1,l'- [carbonyldioxy] dibenzotriazole is a new reactive condensing agent to prepare an active ester for the synthesis of amide. In the literature, 1,l'-[carbonyldioxy] dibenzotriazole was prepared from 1-HOBT and trichloromethyl carbonochloridate. But this reaction has a problem using trichloromethyl carbonochloridate which is more expensive than ethylchloroformate used for BAC preparation and after reaction to give an active ester, generates phosgene(C0Cl2) as a highly toxic agent.Herein, we report the new method preparing an active ester derived from a wboxylic acid using BAC, the mechanism involved in preparing such an active ester, and the amide bond formation using the resulting active ester. BAC (1) was conveniently prepared by reacting 1-HOBT (4)with alkylchlorofonnate under triethylamine in dimethylformamide at O°C (eq.2). The lH-1,2,3-benzotriazol-1-yl ethyl carbonate among BAC, a general formula, was isolated and identified' by comparing its melting point and J R spectrum with those reported in literature'. The results are summarized in the Table 1. These results are the case that all the processes from the preparation of BAC through an active ester (2) to an amide (J), being ...

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ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.