Aging of Bone Marrow Mesenchymal Stromal Cells: Hematopoiesis Disturbances and Potential Role in the Development of Hematologic Cancers

Abstract

Aging of bone marrow is a complex process that is involved in the development of many diseases, including hematologic cancers. The results obtained in this field of research, year after year, underline the important role of cross-talk between hematopoietic stem cells and their close environment. In bone marrow, mesenchymal stromal cells (MSCs) are a major player in cell-to-cell communication, presenting a wide range of functionalities, sometimes opposite, depending on the environmental conditions. Although these cells are actively studied for their therapeutic properties, their role in tumor progression remains unclear. One of the reasons for this is that the aging of MSCs has a direct impact on their behavior and on hematopoiesis. In addition, tumor progression is accompanied by dynamic remodeling of the bone marrow niche that may interfere with MSC functions. The present review presents the main features of MSC senescence in bone marrow and their implications in hematologic cancer progression.

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

“…Age-dependent differences may thus contribute to differences between the present and these previous studies. These could be both age-dependent differences in the AML cells, age-dependent differences in AML supporting stromal cells, e.g., osteoblasts or mesenchymal stem cells and epigenetic alterations [ 90 , 92 , 93 , 94 ]. This may also include an altered metabolism of ATRA in the bone marrow microenvironment [ 95 ].…”

Hematopoiesis during Ontogenesis, Adult Life, and Aging

“…The existing experimental data in this field emphasize the importance of cross-talk between HSCs and MSCs. Aging of MSCs not only affects their behavior but also has a direct impact on hematopoiesis [107]. A clear link between aging, remodeling of the bone marrow microenvironment, and impaired hematopoiesis has been previously demonstrated [140].…”

“…MSCs can only undergo a limited number of cell divisions before entering senescence. Many factors have been described that cause MSC aging, such as oxidative stress [144], shortening of telomeres that occurs during in vitro expansion, and irreparable damage to DNA [107]. The accumulation of senescent cells in aging tissues has also been reported, in particular in a recent study evaluating the expression of p16 and p21, important senescence markers, in donors of various ages [145].…”

“…To fully understand how aging affects hematopoiesis, it is necessary to know how aging alters the biology of HSC and MSC, and how the hematopoietic system compensates its diminished function. An additional aspect in the HSC aging is the fact that HSCs exist in the bone marrow microenvironment, which includes many different types of hematopoietic and nonhematopoietic cells, as well as secreted factors, all of which also accumulate aging-related changes [107]. Aging in the hematopoietic system is thus caused by changes in both the internal properties of HSCs and external signals they receive from the aging organism (Table 2).…”

Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications

“…Other reports have postulated that MSCs maybe a product of long term in vitro culture [102][103][104]. Furthermore, other reports demonstrate bone marrow derived-MSC heterogeneity due to age of donor, with more MSCs from older donors undergoing apoptosis and having a low proliferation rate than those from younger donors [105][106][107]. Naïve MSCs have been shown to exhibit heterogeneity based on transcription data [108].…”