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Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a) ability to regulate secretion of cytokines based on biological need; b) long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c) potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC) in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.

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Cellular therapy for spinal cord injury (SCI) is overviewed focusing on bone marrow mononuclear cells, olfactory ensheathing cells, and mesenchymal stem cells. A case is made for the possibility of combining cell types, as well as for allogeneic use. We report the case of 29 year old male who suffered a crush fracture of the L1 vertebral body, lacking lower sensorimotor function, being a score A on the ASIA scale. Stem cell therapy comprised of intrathecal administration of allogeneic umbilical cord blood ex-vivo expanded CD34 and umbilical cord matrix MSC was performed 5 months, 8 months, and 14 months after injury. Cell administration was well tolerated with no adverse effects observed. Neuropathic pain subsided from intermittent 10/10 to once a week 3/10 VAS. Recovery of muscle, bowel and sexual function was noted, along with a decrease in ASIA score to "D". This case supports further investigation into allogeneic-based stem cell therapies for SCI.

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BACKGROUND: The current paradigm for cord blood transplantation is that HLA matching and immune suppression are strictly required to prevent graft versus host disease (GVHD). Immunological arguments and historical examples have been made that the use of cord blood for non-hematopoietic activities such as growth factor production, stimulation of angiogenesis, and immune modulation may not require matching or immune suppression. METHODS: 114 patients suffering from non-hematopoietic degenerative conditions were treated with non-matched, allogeneic cord blood. Doses of 1-3 x 10(7) cord blood mononuclear cells per treatment, with 4-5 treatments both intrathecal and intravenously were performed. Adverse events and hematological, immunological, and biochemical parameters were analyzed for safety evaluation. RESULTS: No serious adverse effects were reported. Hematological, immunological, and biochemical parameters did not deviate from normal ranges as a result of therapy. CONCLUSION: The current hematology-based paradigm of need for matching and immune suppression needs to be revisited when cord blood is used for non-hematopoietic regenerative purposes in immune competent recipients.

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Induction of tumor-specific immunity is an attractive approach to cancer therapy, however to date every major pivotal trial has resulted in failure. While the phenomena of tumor-mediated immune suppression has been known for decades, only recently have specific molecular pathways been elucidated, and for the first time, rationale means of intervening and observing results of intervention have been developed. In this review we describe major advances in our understanding of tumor escape from immunological pressure and provide some possible therapeutic scenarios for enhancement of efficacy in future cancer vaccine trials.

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The medical significance of circulating endothelial or hematopoietic progenitors is becoming increasing recognized. While therapeutic augmentation of circulating progenitor cells using G-CSF has resulted in promising preclinical and early clinical data for several degenerative conditions, this approach is limited by cost and inability to perform chronic administration. Stem-Kine is a food supplement that was previously reported to augment circulating EPC in a pilot study. Here we report a trial in 18 healthy volunteers administered Stem-Kine twice daily for a 2 week period. Significant increases in circulating CD133 and CD34 cells were observed at days 1, 2, 7, and 14 subsequent to initiation of administration, which correlated with increased hematopoietic progenitors as detected by the HALO assay. Augmentation of EPC numbers in circulation was detected by KDR-1/CD34 staining and colony forming assays. These data suggest Stem-Kine supplementation may be useful as a stimulator of reparative processes associated with mobilization of hematopoietic and endothelial progenitors.

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Patients with congestive heart failure (CHF) that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a) increasing stem cell migration to the heart; b) augmenting stem cell activity; and c) combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.

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The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.

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