Mesenchymal Stem Cells Form 3D Clusters Following Intraventricular Transplantation

Abstract

Mesenchymal stem cells (MSCs) are regarded as an immune privileged cell type with numerous regeneration-promoting effects. The in vivo behavior of MSC and underlying mechanisms leading to their regenerative effects are largely unknown. The aims of this study were to comparatively investigate the in vivo behavior of canine (cMSC), human (hMSC), and murine MSC (mMSC) following intra-cerebroventricular transplantation. At 7 days post transplantation (dpt), clusters of cMSC, hMSC, and mMSC were detected within the ventricular system. At 49 dpt, cMSC-transplanted mice showed clusters mostly consisting of extracellular matrix lacking transplanted MSC. Similarly, hMSC-transplanted mice lacked MSC clusters at 49 dpt. Xenogeneic MSC transplantation was associated with a local T lymphocyte-dominated immune reaction at both time points. Interestingly, no associated inflammation was observed following syngeneic mMSC transplantation. In conclusion, transplanted MSC formed intraventricular cell clusters and exhibited a short life span in vivo. Xenogeneically in contrast to syngeneically transplanted MSC triggered a T cell-mediated graft rejection indicating that MSCs are not as immune privileged as previously assumed. However, MSC may mediate their effects by a "hit and run" mechanism and future studies will show whether syngeneically or xenogeneically transplanted MSCs exert better therapeutic effects in animals with CNS disease.

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

“…In young, healthy mice, it has been reported that MSC administered intracerebroventricularly form cell clusters attached to the ventricle walls [50]. However, in the (See figure on previous page.)…”

“…As discussed above, the protection would exclude cell replacement. Therefore, the effect could be through the production of growth factors or cytokines, vascular effects, reduction of oxidative stress, and modulation of the inflammatory response, as it has been described in other experimental treatments [11,15,50]. Because a heterogeneous population has been transplanted to hydrocephalic hyh mice, more than one effect is expected.…”

BDNF‐overexpressing human mesenchymal stem cells mediate increased neuronal protection in vitro

“…Bone marrow samples were obtained during resection of the femoral head for implantation of a total hip arthroplasty in otherwise healthy donors. Human MSCs were isolated from these samples by density gradient centrifugation and subsequent plastic adhesion of mononuclear cells and cultured as previously described (Hoffmann, Floerkemeier, Melzer, & Hass, ; Jungwirth et al, ).…”

Highly Proliferative Immortalized Human Dental Pulp Cells Retain the Odontogenic Phenotype when Combined with a Beta-Tricalcium Phosphate Scaffold and BMP2

“…Primary antibodies against CD90, CD105, CD34, CD45 (all at 1 : 100, Abcam, Cambridge, MA, USA), and CD73 (1 : 100, BioLegend, San Diego, CA, USA), a goat anti-mouse lgG secondary antibody fluorescent labeled with Alexa Fluor 555 (1 : 1000, Invitrogen, Carlsbad, CA, USA), or a goat anti-rabbit lgG secondary antibody fluorescent labeled with Alexa Fluor 488 (1 : 1000, Invitrogen) was used. Flow cytometry of HDPCs and iHDPCs was performed as described previously [22].…”

“…Stem Cells International 13 Stem Cells International cryopreserved periodontal ligament (PDLSCs), human periapical cyst mesenchymal stem cells (hPCy-MSCs), and oral mucosal progenitor cells [22,24] among which HDPCs are the most common and easily obtained from extracted human teeth. HDPCs successfully regenerate a dentin pulp-like structure in vivo when transplanted with hydroxyapatite/tricalcium phosphate (HA/TCP) powder [25].…”