Plasticity and Tissue Regenerative Potential of Bone Marrow-Derived Cells

Abstract

Diverse in vivo studies have suggested that adult stem cells might have the ability to differentiate into cell types other than those of the tissues in which they reside or derive during embryonic development. This idea of stem cell "plasticity" has led investigators to hypothesize that, similar to embryonic stem cells, adult stem cells might have unlimited tissue regenerative potential in vivo, and therefore, broad and novel therapeutic applications. Since the beginning of these observations, our group has critically examined these exciting possibilities for mouse bone marrow-derived cells by taking advantage of well-characterized models of tissue regeneration, Cre/lox technology, and novel stem cell isolation protocols. Our experimental evidence does not support plasticity of hematopoietic stem cells as a frequent physiological event, but rather indicates that cell fusion could account for reported cases of hematopoietic stem cell plasticity or "transdifferentiation" in vivo. Our studies highlight the need for meticulous technical controls during the isolation, transplantation, tracking, and analysis of bone marrow-derived cells during in vivo studies on plasticity. Further studies will be necessary to better define experimental conditions and criteria to unequivocally prove or reject plasticity in vivo. In this review, we focus on results from several studies from our laboratory, and discuss their conclusions and implications.

Derivation of Neural Stem Cells from Mesenchymal Stem Cells: Evidence for a Bipotential Stem Cell Population

“…These data are compiled from three independent experiments using MSCs derived from different donor samples. is a large body of confl icting results regarding the broader developmental potential of BM and blood stem cells and it remains a controversial issue in the stem cell research fi eld [44][45][46][47].…”

“…We are taking a simplifi ed approach to investigate if BM stem cells can differentiate into neural cells by using a subpopulation of stem cells instead of whole BM or blood cells. It has been reported that all identifi ed stem cell populations in the BM, including hematopoietic stem cells [44][45][46][47], MSCs [21][22][23][24][25][26][27][28], mesodermal adult progenitor cells [50], and others [51][52][53], possess the potential to differentiate into neural cells. However, MSCs are the most well-characterized stem cell population for the generation of neural cells, both in vitro and in vivo, and are the choice of stem cell population in this study.…”

Chirurgische intramyokardiale Stammzelltherapie bei chronischer Myokardischämie

“…Hämatopoetische Vorläuferzellen können bei Zeitverzug bis zur Applikation bei Raumtemperatur gelagert werden, ohne Schaden zu nehmen [24]. Dennoch ist bei offensichtlich hoher Bioverträglichkeit eine Differenzierung in Kardiomyozyten rar [25] und eine Zellfusion mit Kardiomyozyten weitaus wahrscheinlicher [26]. Die Mechanismen, die heute mit den kardioprotektiven Effekten der Zellen in Verbindung gebracht werden, korrelieren weitgehend mit der Steigerung der myokardialen Perfusion und der Reduktion der Apoptoserate im Myokard [27,28].…”

“…Dabei ist der Mechanismus, der dazu führt, dass klinisch nach Injektion von mononukleären Zellen nicht über eine Zunahme von Arrhythmien berichtet wird, noch unklar. Zusammen mit der eher geringen Bereitschaft, zu Kardiomyozyten zu differenzieren [25], ist dies möglicherweise die Folge davon, dass die Zellen nicht über Gap Junctions, sondern durch ihre parakrine Aktivität im Zielgewebe mit den Herzzellen kommunizieren.…”

Passage of bone-marrow-derived liver stem cells in a proliferating culture system

“…About a decade ago, many reports highlighted the broad developmental potential of bone-marrow-derived stem cells [1] . This gave new hope for cell therapy using autologous bone marrow cells, which has few ethical problems and has been applied to severe liver diseases [2] .…”