Challenges in Using Old Tissue and Cells in Treatments

Cell therapies and tissue engineering benefit from being able to use a patient's own cells as a starting point. If the patient is old, as is the case for most potential uses of regenerative medicine, cells are tissues are damaged and dysfunctional. To what degree is this an issue in the construction of treatments? It is clearly killing the patient by degrees, but one of the more promising signs for the near future of stem cell treatments in recent years has been that old stem cells appear to be capable of youthful action given the right cues. The cellular and molecular damage of aging is there, however, and other uses for a patient's own tissues are indeed impacted. This is why the stem cell research field is on a trajectory to understand and reverse aspects of aging in old tissues; they have to do this in order to ensure that the majority of possible treatments will work effectively:

Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments' vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months) and aged (16 months) C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation.

Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants' border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase 9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.



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