Mesenchymal Stem Cells: Time to Change the Name!

Caplan, Arnold I.

doi:10.1002/sctm.17-0051

Cited by 869 publications

(763 citation statements)

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“…Moreover, recently, the change of the name of MSCs into "medicinal signaling cells" were proposed instead of calling as "stem cells" because transplanted MSCs to treat the diseases act their primary beneficial and medicinal function at the injury sites of the body through their secretory action (93). Review | Park et al…”

Section: Environmental Cues Trigger the Secretion Of Paracrine Factorsmentioning

confidence: 99%

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

et al. 2017

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Mesenchymal stem cell (MSC) transplantation represents the next breakthrough in the treatment of currently intractable and devastating neonatal disorders with complex multifactorial etiologies, including bronchopulmonary dysplasia, hypoxic ischemic encephalopathy, and intraventricular hemorrhage. Absent engraftment and direct differentiation of transplanted MSCs, and the "hit-and-run" therapeutic effects of these MSCs suggest that their pleiotropic protection might be attributable to paracrine activity via the secretion of various biologic factors rather than to regenerative activity. The transplanted MSCs, therefore, exert their therapeutic effects not by acting as "stem cells," but rather by acting as "paracrine factors factory." The MSCs sense the microenvironment of the injury site and secrete various paracrine factors that serve several reparative functions, including antiapoptotic, anti-inflammatory, antioxidative, antifibrotic, and/or antibacterial effects in response to environmental cues to enhance regeneration of the damaged tissue. Therefore, the therapeutic efficacy of MSCs might be dependent on their paracrine potency. In this review, we focus on recent investigations that elucidate the specifically regulated paracrine mechanisms of MSCs by injury type and discuss potential strategies to enhance paracrine potency, and thus therapeutic efficacy, of transplanted MSCs, including determining the appropriate source and preconditioning strategy for MSCs and the route and timing of their administration.

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Section: Environmental Cues Trigger the Secretion Of Paracrine Factorsmentioning

confidence: 99%

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

et al. 2017

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Response to: Mesenchymal Stem Cells: Time to Change the Name!

Windt

Vonk

Saris

2017

Stem Cells Translational Medicine

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With great pleasure, we read the recent Perspective by Arnold Caplan in which he urges that we change the name of mesenchymal stem cells (MSCs) to "medicinal signaling cells" [1]. While a name should not be considered an impediment to scientific progress, it is the underlying expectation of the clinical effect of these cells that may encumber the role of MSCs in the field of regenerative medicine. According to the Cambridge dictionary, a stem cell is defined as "a cell, especially one taken from a person or animal in a very early stage of development that can develop into any other type of cell." Because the main functionality of MSCs in vivo is not multipotency, but rather immunomodulatory and trophic, it is argued that we should not call them stem cells after all.We must admit that, when our group started to work with bone-marrow derived MSCs, we called them mesenchymal stem cells because they were able to differentiate into bone, fat, and cartilage in vitro, or at least express the corresponding markers. In aiming at cartilage regeneration, we mixed chondrocytes and MSCs, with the initial hypothesis that the environment would stimulate MSC differentiation [2]. Different groups demonstrated similar results when mixing these cells and incorrectly concluded it was the MSCs that were responsible for the cartilage tissue regeneration [3]. Soon we came to realize that it was not the MSCs that created reproducible cartilage constructs. MSCs were found to induce chondrocytes and stimulate their chondrogenic capacity [4]. We found that preserving the pericellular matrix of chondrocytes (chondrons) enhanced this interaction with MSCs [2]. We also demonstrated that MSCs did not communicate solely through soluble factors, as direct cell-cell contact through gap junctions played an important role in the cellular crosstalk [4]. We and others showed that MSCs disappeared from cocultures while stimulating tissue regeneration [3,5].In his Perspective, Arnold Caplan neatly describes the evolving insight that MSCs are derived from pericytes. Pericytes have been traced in vivo in different tissues and found to retain their original identity [6,7]. It remains unclear, however, how long and exactly through what mechanisms these pericytes stimulate a host response. For example, while trophic factors excreted by MSCs seem to inhibit scar formation and apoptosis, the role of extracellular vesicle excretion and their amelioration of inflammation is only just recently being explored [8]. Although there is evidence that MSCs can remain traceable after several weeks in vivo, it is unclear how implanted cells behave in the human being [9].Based on our clinical work and supported by the signaling cell hypothesis, we assessed the presence of donor DNA from allogeneic MSCs 12 months after implantation in cartilage defects in the knee [10]. In this first-in-human trial, allogeneic MSCs were mixed with autologous recycled chondrons and implanted within a single surgery. DNA analysis using short tandem repeats confirmed our hypothesis that MSCs...

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“…It is worth noting that there are initiatives (spearheaded by Dr. Arnold Caplan) to change the name of exogenously supplied MSCs (in clinical setting) to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative). These cells do not differentiate into neotissue, but stimulate via various biofactors the patient's own site-specific and tissue-specific resident stem cells and progenitors that construct the new tissue [27].…”

Section: Cells As Biomimetic System Componentmentioning

confidence: 99%

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

Gadjanski

2018

Osteochondral Tissue Engineering

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In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE including formation of the OC tissues to be used as high-fidelity disease/ healing models and as in vitro models for drug toxicity/efficacy evaluation are covered. Highlights Biomimetic OC TE uses "smart" scaffolds able to locally regulate cell phenotypes and dual-flow bioreactors for two sets of conditions for cartilage/ bone Protocols for hierarchical OC grafts engineering should entail mesenchymal condensation for cartilage and vascular component for bone Immunomodulation, low oxygen tension, purinergic signaling, time dependence of stimuli application are important aspects to consider in biomimetic OC TE Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering Ivana GadjanskiAbstract In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue en...

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Mesenchymal Stem Cells: Time to Change the Name!

Cited by 869 publications

References 85 publications

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

Strategies to enhance paracrine potency of transplanted mesenchymal stem cells in intractable neonatal disorders

Response to: Mesenchymal Stem Cells: Time to Change the Name!

Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

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