Sunday, October 26, 2008

Microvascular Transplantation After Acute Myocardial Infarction


Benjamin R. Shepherd, PhD, James B. Hoying, PhD, and Stuart K. Williams, PhD
Tissue Engineering, Vol. 13, No. 12, December 2007


Ischemia
: local deficiency of blood supply produced by vasoconstriction or local obstacles to the atrial flow.
Infarction
: tissue that is dying or dead due to deprivation of blood supply.
Graft
: portion of living tissue surgically implanted from one part of an individual to another part of the individual or from one individual to another for its adhesion and growth.
Inosculation
: to connect or join so as to become or make continuous.

Summary: The objective of the study is to evaluate epicardial transplantion of an intact microvascular for the treatment of myocardial ischemia of severe myocardial infarction.


Microvessels from epididymal adipose tissue of rats were isolated and in vitro fragmented between 30 and 500um long. Microvessels (12,000-15,000 fragments/mL) were suspended in cold rat tail type I collagen and other environmental favorable solution. The cell culture is added to wells (0.125mL/well) of 96-well plates with equal volume of bovine serum. The graft (MG) was left to culture for 7 days prior to implantation.


Two groups of rats were used for the experiment: the control group, which received acellular collagen gel transplant, and the experimental group that was transplanted with MG on their left ventricular (LV) epicardium. Initially, both groups had acute myocardial infarction and their LV function was analyzed for later comparison.


After 7 and 14 days of implantation, microvesssels from both groups were isolated and analyzed for vessel density, infarct size, and LV function.

Microvascular grafts (MGs) on the epicardium. Microvessel fragments suspended in a 3-dimensional rat tail type I collagen gel at day 0 (A) undergo extensive endothelial cell sprouting and development of a network of simple microvessels after 7 days in vitro (B). MGs before grafting on the epicardial surface of a mouse having undergone coronary ligation (C). AFter 7 and 14 days of engraftment, the presence of extensive vascularization is readily apparent (D and E). Control graft composed of type I collagen without microvessels remains avascular at 14 days (F).


The microvessel density of the control group was even lower than the pre-implant condition, while the group that received MG implant showed a continuous increase in 14D and 28D time line. The infarct area microvascular density is also analyzed and the area with MG implant has a higher microvascular density than that of controls of infarct alone or the acellular control graft.


MG impanted group were also found to have smaller infarcts than infarct alone or infarct with a cellular control group. The control group demonstrated heart failure, while the group that received the MG implant revived from myocardial ischemia.


Significance: The scientific paper describes microvascular tissue engineering in vitro, which can be transplanted to heal heart muscle infarction. Cardiovascular disease is the leading cause of death in the US. The method described in the study has a great potential to heal many diseases related to the heart and hopefully it will lower the high death rate due to cardiovascular diseases.

4 comments:

James said...

Because of the prevalence in cardiovascular diseases like you mentioned, any new tissue regeneration of the heart could be a major breakthrough. This research seems very promising although a couple points are unclear to me. First of all, what are microvessels? Are they just capillaries that were harvested and fragmented or maybe a special type of them. Also were there any rejection problems, or did were the cultures made using cells from the same individuals? If heart muscle dies rapidly and cultures need to be grown from the patient then it seems like this would not have much clinical use. In any case, this new procedure is useful since it might act as a temporary solution or in the ideal case, a permanent healing process.

Tizita said...

Dear James,

Microvessels are blood vessels harvested for tissue engineering with fragments length in micros. The tissue is extracted from a healthy mice and transplanted into a mice with myocardial ischemia. The main reason being is to avoid pre-existing dysfunction of the native tissue. The source of the microvessels is adipose tissue, which in nature is capable of readily inosculating with a host tissue. As a result, there is no rejection reported upon transplantation of the foreign tissue.

Lavanya said...

You said that the infarct sizes for the experimental mice were smaller than those of control mice after the microvessel implantation. Does this mean that the microvessels caused the infarct tissue to repair? Does the paper talk about the mechanism of how these microvessels are helping infarct tissue? Regardless, this is an exciting breakthrough. The probability of MI patients suffering another MI is relatively high, especially if not treated quickly. While there is much more research to be done here, transplanting microvessels seems to be a simple and great solution.

Tizita said...

Dear Lavanya,

The infract size of the experimental group is smaller than the control due to the implanted intact microvessels repairing the damaged vessels. The mechanism is through the unhealthy tissue successfully integrating the foreign implanted tissue and repairing itself.