Endometrial Regenerative Cells (ERC) are a population of mesenchymal-like stem cells having pluripotent differentiation activity and ability to induce neoangiogenesis. In vitro and animal studies suggest ERC are immune privileged and in certain situations actively suppress ongoing immune responses. In this paper we describe the production of clinical grade ERC and initial safety experiences in 4 patients with multiple sclerosis treated intravenously and intrathecally. The case with the longest follow up, of more than one year, revealed no immunological reactions or treatment associated adverse effects. These preliminary data suggest feasibility of clinical ERC administration and support further studies with this novel stem cell type.
One of the most
important and complex diseases of modern society
is metabolic syndrome. This syndrome has not
been completely understood, and therefore an
effective treatment is not available yet. We
propose a possible stem cell mechanism involved
in the development of metabolic syndrome. This
way of thinking lets us consider also other
significant pathologies that could have similar
etiopathogenic pathways, like lipodystrophic
syndromes, progeria, and aging. All these
clinical situations could be the consequence of
a progressive and persistent stem cell
exhaustion syndrome (SCES). The main outcome of
this SCES would be an irreversible loss of the
effective regenerative mesenchymal stem cells
(MSCs) pools. In this way, the normal repairing
capacities of the organism could become
inefficient. Our point of view could open the
possibility for a new strategy of treatment in
metabolic syndrome, lipodystrophic syndromes,
progeria, and even aging: stem cell
therapies.
Current B-cell disorder treatments take advantage of dose-intensive chemotherapy regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they may lead to insufficient tumor distribution of therapeutic agents, and often cause adverse effects on patients. In this contribution, we propose a novel therapeutic approach in which relatively high doses of Hydroxychloroquine and Chlorambucil were loaded into biodegradable nanoparticles coated with an anti-CD20 antibody. We demonstrate their ability to effectively target and internalize in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53 mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also circulating primary cells purified from chronic lymphocitic leukemia patients. Their safety was demonstrated in healthy mice, and their therapeutic effects in a new model of Burkitt's lymphoma. The latter serves as a prototype of an aggressive lympho-proliferative disease. In vitro and in vivo data showed the ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and Chlorambucil to increase tumor cell killing in comparison to free cytotoxic agents or Rituximab. These results shed light on the potential of anti-CD20 nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a disseminated model of aggressive lymphoma, and lend credence to the idea of adopting this therapeutic approach for the treatment of B-cell disorders.
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