Lung Tissue Engineering Technique with Adipose Stromal Cells Improves Surgical Outcome for Pulmonary Emphysema
Lung Tissue Engineering Technique with Adipose Stromal Cells Improves Surgical Outcome for Pulmonary Emphysema
Link: http://ajrccm.atsjournals.org/cgi/content/abstract/174/11/1199
Lung Tissue Engineering Technique with Adipose Stromal Cells Improves Surgical Outcome for Pulmonary Emphysema is a paper studying and exploring new avenues of tissue engineering of the lung. Problems relating to lung dysfunction include the disease Emphysema. Emphysema, which can be caused by smoking, is a disease characterized by the loss of tissue elasticity which inhibits the function of alveoli, trapping air within the lung, preventing gas exchange with the environment. Symptoms include a shortness of breadth under small amounts of stress. Lung volume reduction surgery (LVRG), which is in essence removal of inefficient tissue, is the main method to correct this disease, but problems incurs in the mending of the remaining lung tissue.
This research group pursed methods of increasing the rate of tissue repair after undergoing LVRG in medical applications. This study has tracked the effects of hepatocyte growth factor (HGF), which induces lung repair and regrowth. Such growth factors are secreted in adipose tissue, specifically by adipose tissue-derived stromal cells (ASCs), which can be found in epidermal tissues. The main question under discernment is whether external cells that are introduced into the wounded area can aid in the reconstruction of the tissue. Addition of the HGF in tissue undergoing surgery can increase efficiency of the lung by increasing the rate of cell growth and stabilize regular function.
The paper described a plethora of experiments to make essential measurements of tissue repair and regrowth. Green florescent protein (GFP) was introduced to mark and label ASCs to see if cells would adhere to a scaffolding. Effects of ASCs attached to a PGAF (polyglycolic acid felt sheet) scaffold were monitored. Rats were used and induced with Emphysema by the introduction of Elastase. As a control, scaffolds without ASCs were used in one set of rats while another set contained ASCs in the scaffold. PCNA antigen introduction was utilized to count cell number. ELISA was used to monitor angiogenesis growth factors (VEGF) and HGF. Laser Doppler was also used to quantify blood flow and capillary density. Blood gas analyzers aided in the measuring of oxygen in the blood at rest. Measurements of oxygen levels were also taken from rats on a treadmill, to monitor performance of the lungs under external stress.
Results of introducing such modified were positive and as expected. ELISA produced results that showed a massive increase in the concentrations of HGF in the ASCs rich scaffolds. Furthermore, cell number also increased as a result of the introduction of stem cells as well as an increase in vascularization and blood flow from the secretion of VEGF and other angiogenic growth factors. On the treadmill experiments, oxygen levels in rats with ASCs were about double than in controlled rats. All in all, these experiments illustrated the success of this lab. Surely the hypothesis was correct and proven.
Future directions include clinical applications. While experiments were done on rats in the laboratory, human experimentations should also be conducted to determine the usefulness in humans and in the medicinal field. More so, investigations concerning age are areas of great consideration. Since lung disease can affect those of all ages, exploration in age dependence must also be traversed. Perhaps using the same techniques and fundamental concepts on other systems in the body can also be explored, and will also lead to favorable results.
This topic is relevant is important because of its implications. With high numbers of smokers world wide, it can be hypothesized that emphysema is a condition that has the potential to make a large impact on human populations. This paper validates the tissue engineering of a new solution by methods beyond just considering the localized tissue engineered zone. While similar techniques in class were used to characterize the performance, other tests concerning the entire specimen in physical endurance tests were also administerd. Thus, one should consider the overall implication of a tissue engineered device. Moreover, this article also validates the implication of tissue engineering in society. For research, it is sometimes difficult to infer the bigger picture of a work. This paper clearly illustrates the identification of a societal issue while posing a novel design for the improvement of post surgical recovery. The evidence of tissue engineering and its success is solidified.
5 comments:
Did the researchers determine the long term effects of using ASC cells on the scaffolds affect the lung tissue? I am just wondering in the cells stop excreting HGF after the lung has recovered from surgery or do they keep on pumping out the growth factor?
Since adipose tissue is rich in many stem cells and other growth factors, are there any side effects in using it as a delivery medium for HGF? Or has there ever been a report where tissue growth was overstimulated and induce fibrous tissue formation?
Also if adipose tissue from healthy individuals was used for the
emphysematous patient, would there be a therapeutic advantage and reduce the chance for future pulmonary emphysema?
Although the researchers did not perform direct long term effects of the ASCs on the scaffold as read in the paper. But an ELISA was performed to study the deposition of HGF proteins as the cells were culturing on a scaffold for seven days. While the data presents what the cells pump out while they are not confluent, they do show that during recovery high amounts of it are produced. Such response, that factors be pumped out could be are regulated by cell-cell interaction. Upon confluency, however,the cells engage in intercellular signaling which would, I believe, would shut down the the gene expression. Thus, it is not likely that the cells would continually produce the growth factors. Rather only during the recovery is where we see a high output of protein.
If you are feeling spiffy, I found this paper:
Autologous Transplantation of Adipose Tissue-Derived Stromal Cells Ameliorates Pulmonary Emphysema
* N. ShigemuraaaDivisions of Cardiothoracic Surgery,
* M. OkumuraaaDivisions of Cardiothoracic Surgery,
* S. MizunobbMolecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Osaka, Japan,
* Y. ImanishiaaDivisions of Cardiothoracic Surgery,
* T. NakamurabbMolecular Regenerative Medicine, Course of Advanced Medicine, Osaka University Graduate School of Medicine, Osaka, Japan and
* Y. Sawaa,*
http://www.blackwell-synergy.com/doi
/abs/10.1111/j.1600-6143.2006.01522.x
(the above addy but all one line)
It suggests that the HGF production does decrease in time from isolation, perhaps due to the fact that there are more cells than what was initially to start out with.
True that there is many other stem cells in adopose tissue, but those stem cells were also took into consideration. As in the paper, "Furthermore, adipose
tissue was also reported to contain an ample source of pluripotent
cells, such as hematopoietic progenitors and spare mesodermal
stem cells, which will differentiate into osteogenic, chondrogenic,
myogenic, and neurogenic lineages (10–14)." So having stem cells in the tissue was planned from the get go. It would help in replenishing the lost tissue in the recovery region. As stated before in the previous comment, there have not been any long term studies to check for overstimulated tissue formation. But, it has been understood that the expression of the proteins are well regulated (see the paper posted above), limiting the chance of haphazard growth.
While cells were transplanted only to recover the lost tissue that was removed from surgery only. Continuation of bad habits, like smoking, will effect the cell again as initially, and will induce emphysema. A healthy person can be described as one who does not smoke, but that does not necessarily make them immune to the effects of smoking. While allogenic transplantations are appealing, one must still consider immunogenic responses, given that the cells are genetically different, which could be bad for the patient, too.
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