Publications by authors named "Frank Zeigler"

Introduction: Bone marrow derived cellular therapies are an emerging approach to promoting therapeutic angiogenesis in ischemic cardiovascular disease. However, the percentage of regenerative cells in bone marrow mononuclear cells (BMMNCs) is small, and large amounts of BMMNCs are required. Ixmyelocel-T, an expanded autologous multicellular therapy, is manufactured from a small sample of bone marrow aspirate.

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Introduction: Advanced atherosclerotic lesions are characterized by lipid accumulation, inflammation, and defective efferocytosis. An ideal therapy should address all aspects of this multifactorial disease. Ixmyelocel-T therapy, an expanded autologous multicellular therapy showing clinical promise in the treatment of diseases associated with advanced atherosclerosis, includes a novel population of M2-like macrophages.

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Introduction: M2 macrophages promote tissue repair and regeneration through various mechanisms including immunomodulation and scavenging of tissue debris. Delivering increased numbers of these cells to ischemic tissues may limit tissue injury and promote repair. Ixmyelocel-T is an expanded, autologous multicellular therapy cultured from bone-marrow mononuclear cells (BMMNCs).

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There is a large body of preclinical research demonstrating the efficacy of gene and cellular therapy for the potential treatment of severe (limb-threatening) peripheral arterial disease (PAD), including evidence for growth and transcription factors, monocytes, and mesenchymal stem cells. While preclinical research has advanced into early phase clinical trials in patients, few late-phase clinical trials have been conducted. The reasons for the slow progression of these therapies from bench to bedside are as complicated as the fields of gene and cellular therapies.

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Aastrom Biosciences has developed a proprietary cell-processing technology that enables the manufacture of ixmyelocel-T, a patient-specific multicellular therapy expanded from a small sample of a patient's own bone marrow. Ixmyelocel-T is produced under current good manufacturing practices (cGMP) in a fully closed, automated system that expands mesenchymal stem cells (MSCs) and macrophages. While the cell types in ixmyelocel-T are the same as those found in the bone marrow, the numbers of MSCs and alternative macrophages are greater in ixmyelocel-T.

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Neural stem/progenitor cells (NSPCs) display inherent pathotropic properties that can be exploited for targeted delivery of therapeutic genes to invasive malignancies in the central nervous system. Optimizing transplantation efficiency will be essential for developing relevant NSPC-based brain tumor therapies. To date, the real-world issue of handling and affixing NSPCs in the context of the neurosurgical resection cavity has not been addressed.

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The central nervous system (CNS) is composed of multiple cell types formed through a process of lineage commitment and phenotypic differentiation of stem-like progenitor cells into three key cell types: neurons, astrocytes, and oligodendrocytes. The ability to isolate and culture these CNS stem/progenitors has facilitated the characterization of the molecular mechanisms that regulate this process, in the hopes of providing therapeutically effective cells to treat disease and injury. Although astroglial, and to a lesser extent some neuronal, phenotypes are robustly generated when these cultured stem/progenitor cells are induced to differentiate, oligodendrocytes that form the myelin-rich sheath that allows nerves to conduct action potentials are only formed at a low frequency.

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