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Tan J.L.,Monash Institute of Medical Research | Chan S.T.,Monash Institute of Medical Research | Lo C.Y.,Monash University | Deane J.A.,Monash Institute of Medical Research | And 8 more authors.
Stem Cell Research and Therapy | Year: 2015

Introduction: The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study, we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury. Methods: Either CD45+/FoxP3+ Tregs or CD45+/FoxP3 - non-Tregs were adoptively transferred into Rag1 -/- mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later. Results: Mitigation of lung inflammation and fibrosis was observed only in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be transforming growth factor-beta (TGFβ)-dependent. Furthermore, polarisation of macrophages from M1 to M2 occurred only in animals that received hAECs and Tregs. Conclusions: This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages, and T-cell subsets is central to understanding the mechanisms by which hAECs elicit lung repair. © 2015 Tan et al.; licensee BioMed Central. Source


Santini M.P.,Imperial College London | Santini M.P.,Heart Science Center | Rosenthal N.,Imperial College London | Rosenthal N.,Australian Regenerative Medicine Institute
Journal of Cardiovascular Translational Research | Year: 2012

The capacity to regenerate damaged tissue and appendages is lost to some extent in higher vertebrates such as mammals, which form a scar tissue at the expenses of tissue reconstitution and functionality. Whereas this process can protect from further damage and elicit fast healing, it can lead to functional deterioration in organs such as the heart. Based on the analyses performed in the last years, stem cell therapies may not be sufficient to induce cardiac regeneration and additional approaches are required to overcome scar formation. Among these, the immune cells and their humoral response have become a key parameter in regenerative processes. In this review, we will describe the recent findings on the possible therapeutical use of progenitor and immune cells to rescue a damaged heart. © 2012 The Author(s). Source


News Article
Site: http://www.rdmag.com/rss-feeds/all/rss.xml/all

Australian scientists have developed a new method for harvesting stem cells, which is less invasive and reduces side effects for donors. For bone marrow transplantation, stem cells are routinely harvested from healthy donors and used to treat patients with cancers including leukaemia. Current harvesting methods take a long time and require injections of a growth factor to boost stem cell numbers. This often leads to side effects. The discovery, published today in Nature Communications, reduces the time required to obtain adequate numbers of stem cells, without the need for a growth factor. The method, developed by a team of CSIRO researchers working within the manufacturing arm of CSIRO with the Australian Regenerative Medicine Institute (ARMI) at Monash, combines a newly discovered molecule (known as BOP), with an existing type of molecule (AMD3100) to mobilise the stem cells found in bone marrow out into the blood stream. CSIRO researcher Susie Nilsson, who holds a doctorate in Pathology, said her team was able to demonstrate that combining the two molecules directly impacts stem cells so they can be seen in the blood stream within an hour of a single dosage. "Current treatment requires the patient to have growth factor injections for several days leading up to the procedure," Nilsson said. "Using the new method eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour." Until now AMD3100 has only been effective in increasing stem cell numbers when combined with the growth factor. "But the growth factor can cause unpleasant side effects like bone pain and spleen enlargement for some patients," Nilsson added. "Other patients simply don't respond well, and their stem cell count never gets high enough for a successful transplant." The scientists found that combining the two small molecules not only eliminates the need for the growth factor, but when the harvested cells are transplanted they can replenish the entire bone marrow system, and there are no known side effects. Professor Peter Currie, ARMI Director, said a major benefit of the discovery is that harvesting stem cells will become more efficient and effective, considerably reducing the stress for donors. "We're looking forward to seeing patients benefit from this discovery," Professor Currie said. So far successful pre-clinical studies have demonstrated the effectiveness of the treatment. The next step is a phase 1 clinical trial assessing the combination of BOP molecule with the growth factor, prior to the eventual successful combination of the two small molecules BOP and AMD3100.


News Article
Site: http://www.biosciencetechnology.com/rss-feeds/all/rss.xml/all

Australian scientists have developed a new method for harvesting stem cells, which is less invasive and reduces side effects for donors. For bone marrow transplantation, stem cells are routinely harvested from healthy donors and used to treat patients with cancers including leukemia. Current harvesting methods take a long time and require injections of a growth factor to boost stem cell numbers. This often leads to side effects. The discovery, published today in Nature Communications, reduces the time required to obtain adequate numbers of stem cells, without the need for a growth factor. The method, developed by a team of CSIRO researchers working within the manufacturing arm of CSIRO with the Australian Regenerative Medicine Institute (ARMI) at Monash, combines a newly discovered molecule (known as BOP), with an existing type of molecule (AMD3100) to mobilise the stem cells found in bone marrow out into the blood stream. CSIRO researcher Dr. Susie Nilsson said her team was able to demonstrate that combining the two molecules directly impacts stem cells so they can be seen in the blood stream within an hour of a single dosage. "Current treatment requires the patient to have growth factor injections for several days leading up to the procedure," Dr Nilsson said. "Using the new method eliminates the need for this, meaning a procedure that once took days can be reduced to around an hour." Until now AMD3100 has only been effective in increasing stem cell numbers when combined with the growth factor. "But the growth factor can cause unpleasant side effects like bone pain and spleen enlargement for some patients," Dr Nilsson said. "Other patients simply don't respond well, and their stem cell count never gets high enough for a successful transplant." The scientists found that combining the two small molecules not only eliminates the need for the growth factor, but when the harvested cells are transplanted they can replenish the entire bone marrow system, and there are no known side effects. Professor Peter Currie, ARMI Director, said a major benefit of the discovery is that harvesting stem cells will become more efficient and effective, considerably reducing the stress for donors. "We're looking forward to seeing patients benefit from this discovery," Professor Currie said. So far successful pre-clinical studies have demonstrated the effectiveness of the treatment. The next step is a phase 1 clinical trial assessing the combination of BOP molecule with the growth factor, prior to the eventual successful combination of the two small molecules BOP and AMD3100.


Lexow J.,Imperial College London | Poggioli T.,Imperial College London | Rosenthal N.,Imperial College London | Rosenthal N.,Australian Regenerative Medicine Institute | And 2 more authors.
Recent Patents on Regenerative Medicine | Year: 2013

The mammalian heart has a limited capability of physiological cardiomyocyte turnover during adult life to substitute aged or damaged cells. While this regenerative mechanism has been preserved throughout mammalian evolution, it is insufficient to counteract more extensive tissue loss, which results in scar formation at the expense of cardiac function. In recent years, regenerative medicine studies investigated the efficiency of stem cells to regenerate the heart via cell-therapy, while pre-conditioning the hostile environment of the injured cardiac tissue by administration of cell survival and anti-inflammatory molecules. Indeed, post-infarct combinatorial therapies using cells and factors (including growth factors, chemokines and cytokines) increased cardiac function recovery and tissue regeneration. In addition, the use of factors and molecules capable of inducing adult cardiomyocytes to re-enter cell cycle was explored to overcome the intrinsic cell cycle block or the loss of mitogenic stimuli in the postnatal heart. Nevertheless, the field has yet to solve significant obstacles including the incomplete differentiation of stem cells (with the associated danger of tumor formation) and the paucity of tissue-specific stem cells (specifically in adult/aged organs). In this review, we describe the advances in cardiac regenerative studies and the patented designs of new tools to heal an injured heart. © 2013 Bentham Science Publishers. Source

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