Читать книгу PRF Applications in Endodontics - Mahmoud Torabinejad - Страница 13

First isolated in bone marrow, bone marrow–derived MSCs were found to be precursors to multiple cell types and could be viably cultured while retaining their capacity for multilineage differentiation. Obtained from an invasive bone marrow harvesting procedure, bone marrow–derived MSCs avoid the ethical concerns as well as tumorigenicity of embryonic stem cells and have subsequently been used in a nearly exponential increase in research studies and trials.2 Unfortunately, bone marrow–derived MSCs are relatively low yield and limited to autologous use, requiring in vitro expansion that increases the risk of contamination. Additionally, harvesting the cells requires a surgical procedure with associated donor morbidity and risk, and the potency (ie, “stemness”) has been questioned when compared with more recently discovered sources of MSCs.3

One of these sources is umbilical cord blood (also known as cord blood), collected via venipuncture of the typically discarded umbilical cord. Painless and without morbidity, cord blood is considered superior to human bone marrow stem cells in its harvesting and yield. Cord blood is cryopreserved in two main methods using dimethyl sulfoxide (DMSO): (1) red cell reduction, which is less expensive to store and easier to defrost; and (2) plasma depletion, which is more economical to process. Public cord blood banks cost about $1,500 to $2,500 per unit stored, while private banks typically charge an initial processing fee of $1,400 to $2,300 plus annual storage costs of $115 to $150. However, MSCs only represent a small proportion—1,000 to 5,000 MSCs in one 100-mL unit of cord blood—of the cell types within cord blood, which includes hematopoietic cell types, endothelial and progenitor cells, as well as MSCs.4

There has also been recent attention toward Wharton’s jelly (WJ) within umbilical cords. WJ was found at the turn of the century to contain a multipotent, fibroblast-like MSC population with greater multipotent potency, faster proliferation, and longer life spans than adult bone marrow–derived MSCs.3 This is a result of reduced telomere length. Telomeres shorten with age, eventually resulting in cellular senescence. MSCs isolated from cord blood are much younger than adult MSCs and possess significantly longer telomeres.5

MSCs in WJ are an entity apart from cord blood MSCs and endothelial cells from the umbilical vein. The plentiful presence of MSCs in WJ is theorized to either be due to the trapping and retaining of fetal MSCs during the two waves of migration of fetal MSCs in early development or to the fact that the cells in WJ are actually primitive MSCs that originate from mesenchyme already present in the umbilical cord matrix. More research has been focused on not only the characterization and usage of these WJ-derived MSCs, but also on discrete differences of the stem cell populations depending on the anatomical region of the WJ.6

The most recent development is that what was once thought to be a single mass providing uniform MSCs is actually more anatomically distinct. There are six different zones of the cord with cells in various stages of differentiation: (1) the surface (amniotic) epithelium, (2) subamniotic stroma, (3) clefts, (4) intervascular stroma, (5) perivascular stroma, and (6) vessels. However, the descriptors separating these zones are not clear. It is thought that WJ is composed mainly of perivascular progenitors but may possibly include nonperivascular progenitors as they move away from the vasculature.6 In addition to the anatomical differences, there is concern that the MSCs may differ lengthwise and that the mother end of the umbilical cord may have different mesenchymal features than the fetus end of the umbilical cord.7

In addition to harvesting and potency advantages, cord blood and WJ-derived MSCs are also not limited to autologous use. Due to their excellent immunomodulatory properties and universally tolerated surface marker profiles, MSCs isolated from cord blood and WJ can be made available to patients as allografts.8^,9 Using cells isolated from birth tissue as “off-the-shelf” allografts greatly simplifies the manufacturing process of MSCs for therapeutic use, providing a standardized, scalable method of producing cells that does not need to be personalized for each patient.