Two steps to functional mesenchymal stromal cells for clinical application

Bartmann, Christina; Rohde, Eva; Schallmoser, Katharina; Pürstner, P.; Lanzer, Gerhard; Linkesch, Werner; Strunk, Dirk

doi:10.1111/j.1537-2995.2007.01219.x

Cited by 117 publications

(90 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Bone marrow-derived mesenchymal stem cells (MSCs) possess numerous desirable characteristics for clinical application given their relatively hypo-immunogenic profile [14][15][16][17][18] as well as their ease of isolation, expansion capacity and amenability to genetic manipulation [19][20][21][22] . Importantly, stereotaxic injection of autologous MSCs to Parkinson's disease patients in an open-label trial was not associated with any serious adverse events 23 and highlights the advanced phase that this novel therapeutic concept has reached in a relatively short time frame.…”

Section: Text Introductionmentioning

confidence: 99%

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain

Moloney

Fhlathartaigh

Kulkarni

et al. 2015

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

Treatment of neurodegenerative disease is entering a new era where direct intracerebral delivery of therapeutic factors aims to restore normality to dysfunctional circuits.Cell-based therapeutic approaches, where virally manipulated mesenchymal stem cells (MSCs) over-expressing glial cell line derived neurotrophic factor (GDNF) are utilised as vehicles to deliver neurotrophic support to the Parkinsonian brain, have shown promising pre-clinical results at preserving dopaminergic neuron integrity. However, poor cell survival following transplantation will hinder clinical progression. One approach to improve MSCs survival following transplantation is to couple the cell engraftment procedure with a scaffold thereby providing a physical substrate upon which to eventually complex pro-survival factors. Evaluation of commercially available, clinically accepted materials with an established safety profile will expedite clinical translation. Therefore, this study sought to determine if a clinically used fibrin scaffold can be utilised as an adjunct to intra-cerebral cell transplantation without evoking an adverse host or stem cell response. Sixteen male SpragueDawley rats received bilateral intra-striatal transplants of 30,000 GDNF-transduced MSCs delivered in either control transplantation medium or a fibrin scaffold. Rats were sacrificed 1, 4, 7, and 14 days post-transplantation. Brains were analysed to determine in situ polymerisation and biodegradability of the fibrin scaffold, GDNF release from transplanted GDNF-MSCs, survival of the GDNF-MSCs graft and the host's immune response to the transplant. This study found that fibrin scaffold was adaptable to intra-cerebral delivery with successful polymerisation of the fibrin scaffold in situ. Inclusion of the fibrin scaffold was not detrimental to cell survival nor did it impede neurotrophin release from entrapped cells.Importantly, the inclusion of the fibrin scaffold was associated with a reduced host astroglial and microglial response compared to cells alone indicative of a favourable biocompatibility profile. Overall, fibrin represents an adaptable scaffold for inclusion in a minimally invasive cell-based therapeutic approach for neurodegenerative diseases.TEXT Introduction:

show abstract

Section: Text Introductionmentioning

confidence: 99%

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain

Moloney

Fhlathartaigh

Kulkarni

et al. 2015

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

show abstract

“…A more standardized method for the isolation of MSC can be facilitated by a two-step protocol in which cells are seeded at a low cell density of only 10 cells per cm 2 . 8 Furthermore, fetal bovine serum (FBS) can be replaced by pooled human platelet lysate (pHPL) 9 or thrombin-activated platelet-rich plasma 10 to exclude contamination of the cell product by bovine prions, viruses or other xenogeneic agents. Nonetheless, all methods result in heterogeneous cell preparations and reliable markers for the definition of the multipotent subsets have so far been elusive.…”

Section: Introductionmentioning

confidence: 99%

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Schallmoser¹,

Bartmann²,

Rohde³

et al. 2010

Haematologica

108

View full text Add to dashboard Cite

BackgroundResearch on mesenchymal stromal cells has created high expectations for a variety of therapeutic applications. Extensive propagation to yield enough mesenchymal stromal cells for therapy may result in replicative senescence and thus hamper long-term functionality in vivo. Highly variable proliferation rates of mesenchymal stromal cells in the course of long-term expansions under varying culture conditions may already indicate different propensity for cellular senescence. We hypothesized that senescence-associated regulated genes differ in mesenchymal stromal cells propagated under different culture conditions. Design and MethodsHuman bone marrow-derived mesenchymal stromal cells were cultured either by serial passaging or by a two-step protocol in three different growth conditions. Culture media were supplemented with either fetal bovine serum in varying concentrations or pooled human platelet lysate. ResultsAll mesenchymal stromal cell preparations revealed significant gene expression changes upon long-term culture. Especially genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all mesenchymal stromal cell preparations. ConclusionsLong-term cell growth induced similar gene expression changes in mesenchymal stromal cells independently of isolation and expansion conditions. In advance of therapeutic application, this panel of genes might offer a feasible approach to assessing mesenchymal stromal cell quality with regard to the state of replicative senescence.

show abstract

“…CD14 purity was checked by flow cytometry (supplementary Figure S1). BM-derived MSC were isolated in alpha-modified Eagle's medium (α-MEM; Sigma-Aldrich, St Louis, MO, USA) via plastic adherence (17,18). Primary EPC, also called endothelial colony-forming progenitor cells (ECFC), were directly recovered from heparinized but otherwise unmanipulated PB by plastic adherence in endothelial growth medium (EGM-2; Lonza, Walkersville, MD, USA) (19).…”

Section: Methodsmentioning

confidence: 99%

“…Magnetically sorted monocytes (CD14 purity 97.9-99.3%; supplementary Figure S1), EPC and MSC containing less than 1% hematopoietic contamination (17,26,27) The number and size of Nile Red-stained LD/cell further increased after pro-angiogenic induction plus an extended acLDL exposure (condition IV, 102 LD/cell) even though monocytes were not differentiated into macrophages using external macrophage-colonystimulating factor (M-CSF) induction. In contrast, EPC and MSC entirely lacked LD accumulation in all lipid exposure conditions (Figure 2A, rows 3-6), as well as in control cultures (Figure 2A, row 7).…”

Section: Foam Cells Develop From Human Monocytes In Vitromentioning

confidence: 99%

“…This may be even more relevant if pro-atherogenic pathologic conditions at the time of treatment are sustained. Over the last few years, we and others have developed procedures to isolate and propagate hematopoietic, endothelial and mesenchymal precursors for therapeutic application (16)(17)(18)(19)(20)(21)(22). Therapy with specifically manipulated cells to promote tissue vascularization and repair after organ damage is a central goal of regenerative medicine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pro-angiogenic induction of myeloid cells for therapeutic angiogenesis can induce mitogen-activated protein kinase p38-dependent foam cell formation

et al. 2011

Self Cite

View full text Add to dashboard Cite

Background aims-Clinical trials for therapeutic angiogenesis use blood-or bone marrowderived hematopoietic cells, endothelial progenitor cells (EPC) and mesenchymal stromal cells (MSC) for vascular regeneration. Recently concerns have emerged that all three cell types could also contribute to atherosclerosis by foam cell formation. Therefore, we asked whether human myelomonocytic cells, EPC or MSC can accumulate lipid droplets (LD) and develop into foam cells.

show abstract

Two steps to functional mesenchymal stromal cells for clinical application

Cited by 117 publications

References 42 publications

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain

Fibrin As a Scaffold for Delivery of GDNF Overexpressing Stem Cells to the Adult Rat Brain

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Pro-angiogenic induction of myeloid cells for therapeutic angiogenesis can induce mitogen-activated protein kinase p38-dependent foam cell formation

Contact Info

Product

Resources

About