Discover the Regenerative Potential of Exosomes
blood vessels. Perinatal MSC exosomes have also demonstrated efficacy in preserving the viability of damaged cells, which has the effect of preventing apoptosis and necrosis. In severely damaged tissues that do not survive, these exosomes reduce the extent of fibrosis and scarring in the healing tissues. Perinatal MSC exosomes have also shown suppression of tumor growth in pre-clinical models that have been studied. It is important to note that these biologic properties may be related to one or more of the proteins, as well as the micro RNAs contained within these exosomes. One of the most important points to understand, when considering the biologic properties of perinatal MSC exosomes, is that their effects are not the result of any single protein, mRNA or micro RNA that is contained within the exosomes. Instead, the biologic properties of these exosomes result from the combined effects of hundreds of proteins, mRNAs and micro RNAs acting in concert on multiple signaling pathways and having direct effects within the target cell. The composite effect of these exosomal signaling factors sometimes causes predictable effects based on the exosome constituents. At other times exosomes may exhibit paradoxical effects that cannot be easily explained by the well understood biologic activity of their individual contents. In the case of perinatal MSC exosomes, they appear to have positive net biologic effects across the models of injury and disease that have been studied in vitro and in vivo. One explanation for the beneficial biologic properties of perinatal MSC exosomes exert may be related to their role in nature. The natural function of perinatal MSC exosomes is to support the development of the fetus. A central function in this regard is to promote the rapid, controlled cell proliferation that underlies growth. These exosomes also play a role in suppressing inflammation in utero to allow the pregnancy to be carried to term, and modulating the maternal immune system to prevent rejection of the fetus. Supporting the development of connective tissues and their blood supply are also important roles of perinatal MSC exosomes. Finally, these exosomes participate in the suppression of oncogenesis by controlling the growth of the rapidly dividing cells. The biologic properties of perinatal MSC exosomes differ from those of adult MSC exosomes. The closest analog to mesenchymal stem cells in the adult are progenitor cells that may be harvested from bone marrow or fat. These adipose-derived
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or bone marrow-derived stromal cells behave differently and produce exosomes with different contents than perinatal MSCs because of the age-associated decline in the numbers and level of function of these senescent progenitor cells. For example, at birth there are about 1 in 10,000 MSCs in bone marrow, while at age 20, there are about 1 in 100,000 MSCs in bone marrow. These senescent progenitor cells also express different proteins and miRNA than perinatal MSCs. One familiar example of this loss of protein expression may be illustrated by the reduction in lactase expression in adults, which results in lactose intolerance in many adults. Another clinically relevant example of the loss of protein expression in adult cells is the reduced expression of tumor suppressor proteins, which explains why many cancers are frequently diagnosed later in life. Finally, recent cataloguing of micro RNA present in circulating microvesicles indicates that the levels of specific micro RNAs change with aging or in specific disease states. Tissue-derived exosomes also differ from isolated, perinatal MSC exosomes for several reasons, one of which is that sampling tissues for exosomes yields a multitude of different exosomes produced by different cell types, which differ significantly in their contents and corresponding biologic properties. MSC exosomes constitute only a very small fraction of the population of exosomes and other biologic material in both adult and perinatal tissues. In order to concentrate MSC exosomes from composite perinatal tissue, different methods may be employed. One such method is sterile filtration, which can remove cells and other larger particulate material from the samples, but unfortunately leaves nano-particulate debris with similar size and density to the exosomes along with the entire fraction of exosomes produced by different cell types. One example of particulate contamination that may persist after this type of filtration may be ABO blood type incompatibility antibodies, which could cause lifethreatening complications, if unknowingly administered along with exosomes. Another method for MSC exosome isolation is antibody-coated bead extraction, which uses antibodies that bind to MSC exosome membrane proteins to separate these exosomes from the other biologic material in tissues. Unfortunately, the antibody remains attached to the exosome after this separation, creating the potential to trigger an immune response. Compared with both of these methods,isolated MSC exosomes can be much more safely and effectively harvested from isolated MSC cultures, which virtually eliminates the potential for contamination with particulate biologic material and infectious agents.
ANTI-AGING MEDICAL NEWS
• SUMMER 2020
