Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy

Abstract

Multipotential mesenchymal stromal cells (MSC) are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration. In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage, or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-vs.-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage. Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies?

Identification and Characterization of a Large Source of Primary Mesenchymal Stem Cells Tightly Adhered to Bone Surfaces of Human Vertebral Body Marrow Cavities

“…We also have successfully isolated these cells from older donors (up to 56 years) and demonstrated expansion in culture (unpublished data). However, we intentionally focused on young donors in this report given the literature suggesting higher frequencies and proliferation rates of MSC derived from various tissues obtained from young donors compared to their older counterparts [49][50][51][52][53][54][55]. Therefore, in the absence of impacts from environment and disease status, the lowest COG to manufacture vBA-MSC would be from young donors.…”

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

“…The potency of mesenchymal stem cells exhibits significant age and donor variation [3,[184][185][186].…”

“…A robust potency assay has been established based on pooling responder leukocytes to minimize individual immune response variability. It has highlighted significant donor variation of human mesenchymal stem/progenitor cell immune modulatory capacity and extended radioresistance [184,185].…”

The molecular mechanisms of action of PPAR-γ agonists in the treatment of corneal alkali burns?(Review)

“…Limbal transplantation is a standard procedure to restore ocular surface disorders and, considering the shortage of corneal donors, is a viable alternative treatment strategy; however, the success rate remains low ( 20 ). Additionally, the separation and purification rates of limbal cells and the efficiency of migration require further investigation, and the therapeutic efficacy and safety of limbal transplantation should be clarified ( 21 ). Furthermore, the rejection rate of keratoplasty is high in cases of CAB, and the number of suitable donor corneas available is not sufficient to meet the demands ( 22 , 23 ).…”