Perspective: Is It Time to Rename MSC (Mesenchymal Stem Cells/Medicinal Signaling Cells) with a Name that Reflects Their Combined <i> In Vivo </i> Functions and Their <i> In Vitro </i>Abilities?—Possibly “Pluripotent Mesenchymal Regulatory Cells (PMRC)”

Abstract

Over 30 years ago, it was reported by Caplan that cells could be found in various adult tissues and fluids of a variety of species that could be induced in vitro to progress towards lineages such as chondrogenesis, osteogenesis and adipogenesis with different "cocktails" of reagents. These cells were called Mesenchymal Stem Cells (MSC) to reflect this pluripotency. After 30 years of intense research effort to directly use such cells for the repair or regeneration of damaged or injured tissues, the effort has met with limited in vivo success, but their use for in vitro tissue engineering has met with some success. This failure to live up to expectations for in vivo differentiation success has led Caplan to recently rename these cells Medicinal Signaling Cells (MSC) to reflect other abilities of these cells to secrete mediators and release exosomes containing biologically active molecules that can influence their neighboring cells in a paracrine manner. However, neither of these names completely captures the combined apparent in vivo functioning of MSC and their in vitro abilities to exhibit pluripotent behavior. Thus, it is suggested, based on the attributes of these cells and their tissue and clonal heterogeneity, that an alternative name be applied to these cells and they be described as Pluripotent Mesenchymal Regulatory Cells (PMRC). This name reflects their regulatory function as pericytes in tissues, as well as their well-known immunoregulatory activity when injected into the intra-articular space and their influence on activities such as

One of the Primary Functions of Tissue-Resident Pluripotent Pericytes Cells May Be to Regulate Normal Organ Growth and Maturation: Implications for Attempts to Repair Tissues Later in Life

“…Partly due to the challenges faced, Caplan [ 21 ] then suggested changing the name from mesenchymal stem cells (MSC) to medicinal signaling cells (MSC) to indicate their potential primary role in the adult to be a source of biologic signals via secretions or release of extracellular vesicles [ 126 ]. As this definition did not capture the pluripotency of the cells, it was further suggested by Hart [ 32 ] that the cells be called pluripotent mesenchymal regulatory cells (PMRC) to account for both the pluripotency and signaling properties of the cells.…”

“…Being integrated into the unique environment of a tissue or organ at an early age, as well as being positioned in close proximity to the microvascular component, and capable of secreting relevant molecules as well as regulated “shedding” exosomes or extracellular vesicles containing relevant molecules that can migrate to target cells in a paracrine manner, make the cells currently called MSC ideal candidates to “translate” generalized anabolic factors in the bloodstream during growth and development into signals that are more organ- or tissue-relevant or impactful to a coordinated growth and maturation of each tissue or organ to retain function during periods of transition as in growth and development. Thus, these cells that have been called MSC may more appropriately be called Pluripotent Mesenchymal Regulatory Cells (PMRC) [ 32 ], a term that captures both the differentiation and signaling functions and abilities of MSC when becoming tissue-specific pericytes rather than using two different terms as suggested by Caplan [ 21 , 22 ]. In such a role, the pluripotent aspects of their capabilities may have benefits in maintaining tissue integrity via their self-renewal potential, as well as their ability to replace cells that have died via apoptosis or via errors in replication, and their ability to secrete tissue-specific mediators and release extracellular vesicles.…”

“…When this effort did not lead to the expected success, Caplan [ 21 ] suggested a name change to Medicinal Signaling Cells with the abandonment of the term Stem Cells. However, this did not address the pluripotency of the cells or the fact that the lineage-specific differentiation was not important in and of itself other than to confirm that the cells had pluripotency abilities [ 32 ]. The present discussion would suggest that the pluripotency of the cells is critical for the ability of the cells in question to adapt and integrate into each organ system in an organ-specific manner, leading to the coordinated growth and maturation of each organ with the retention of their integrated functioning.…”

“…One should not dismiss the pluripotency of these cells from the name [ 3 ]. This conundrum has led to the suggestion that perhaps what have been called MSC should be renamed Pluripotent Mesenchymal Regulatory Cells (PMRC) to reflect their in vivo function associated with being organ-specific pericytes and their in vitro pluripotency [ 32 ]. The current review is focused on the possibility that in vivo, the pericyte function and the pluripotency of these cells are integrated during growth and maturation to facilitate the coordinated growth of organs and the integration of their cellular complement to yield a functioning system that can respond to systemic modulators of growth and maturation.…”

Creating an Optimal In Vivo Environment to Enhance Outcomes Using Cell Therapy to Repair/Regenerate Injured Tissues of the Musculoskeletal System

“…Differences in the ability to differentiate towards the different lineages were noted between cells isolated from different locations [ 122 , 123 , 124 ]. However, MSC isolated from individual tissues demonstrates extensive heterogeneity, discussed in [ 123 , 124 , 125 ].…”