Regenerative Medicine Utrecht

Jacqueline Alblas, PhD

Assistant Professor
Orthopaedics
RMCU, UMC Utrecht
j.alblas@umcutrecht.nl

Our research requires intense integration of
immunology and orthopaedics.


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As PI bone regeneration within the Orthopaedics department, my research activities have focused on development of bone replacement constructs, in which scaffold material and cell stimuli are optimally combined with the regenerative potential of adult stem cells. To achieve this, our activities evolve around specific topics and technological achievements.

Printing of living cells, which we developed in our lab, has expanded our knowledge on cell fate and osteogenicity in 3D tissue constructs. Bioprinted constructs are used to investigate the role of self-organization of cells and matrix components in tissue repair and are successfully implanted in preclinical studies. Furthermore, bioprinted constructs serve as 3D models, such as the reconstituted bone marrow niche used to study bone-residing malignancies.

Vascularization in bone constructs is highly needed for survival and is optimized using strategies involving endothelial progenitor cells and controlled delivery of growth factors, combined with bioprinting. Growth factor delivery by means of gene-activated matrices has led to efficient bone induction in small and large animal models, and is given effort for translation to the clinic.

The interaction of bone with the immune system is an important subject, in particular with respect to the use of allogeneic cells and the influence of immune cells and inflammatory mediators on bone regeneration.

Other activities: Board member NBTE (Netherlands Society for Biomaterials and Tissue Engineering); Member AO Research Review Commission; Editorial Board of Bioengineering; Member TERMIS.

Course director/lecturer within Medicine and Biomedical Sciences curriculi (BA/MA), University Utrecht Graduate School of Life Sciences, Regenerative Medicine programme; co-organiser/speaker at diverse international conferences.

Research
Bioprinting the bone marrow niche for multiple myeloma
The bone marrow (BM) niche has an essential role in supporting hematologic malignancies including multiple myeloma (MM). The progression of MM depends on signals and cell-cell interactions provided by the surrounding BM niche, which facilitates cell homing and proliferation. Primary MM cells cannot survive outside the BM, and thus cannot be expanded on their own. We have developed an easy-to-use, controllable, and reproducible three dimensional (3D) BM model which mimics the natural MM environment. Both a vascular compartment and an osteogenic compartment have been designed and investigated for their supportive potential towards primary CD138+ MM cells.

Both compartments of the model are capable of facilitating CD138+ MM cell survival during 4 weeks. The modelwas validated by showing that interactions of MM cells with the surrounding microenvironment recapitulated the patient situation.

Interactions between the immune system and bone
Local immune responses are known to direct bone healing or regeneration, but the role of T lymphocytes is elusive. The results of our experiments indicate that activated T cells are regulators of osteoblast maturation through the production of soluble factors. Moreover, individual T helper cell subsets differentially control MSC osteogenesis. We found that pro-inflammatory T lymphocyte populations, including the Th17 cells, are highly stimulatory for bone osteogenic differentiation. The occurrence of different T cells may be a predictive factor for bone healing in patients.

Selected literature
Pubmed search: Alblas J

  1. Wegman F, Poldervaart MT, van der Helm YJ, Oner FC, Dhert WJ, Alblas J. Combination of bone morphogenetic protein-2 plasmid DNA with chemokine CXCL12 creates an additive effect on bone formation onset and volume. Eur Cell Mater. 2015 Jul 27;30:1-10.
  2. Poldervaart MT, Gremmels H, van Deventer K, Fledderus JO, Oner FC, Verhaar MC, Dhert WJ, Alblas J. Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaffolds with defined architecture. J Control Release. 2014 Jun 28;184:58-66.
  3. Loozen LD, Wegman F, Oner FC, Dhert WJA and Alblas J. Porous bioprinted constructs in BMP-2 non-viral gene therapy for bone tissue engineering. Journal of Materials Chemistry B, 2013. 1:48, 6619-6626.
  4. Wegman F, van der Helm Y, Öner FC, Dhert WJ, Alblas J. Bone morphogenetic protein-2 plasmid DNA as a substitute for bone morphogenetic protein-2 protein in bone tissue engineering. Tissue Eng Part A. 2013 Dec;19(23-24):2686-92.
  5. Fedorovich NE, Alblas J, Hennink WE, Oner FC, Dhert WJ. Organ printing: the future of bone regeneration? Trends Biotechnol. 2011 Dec;29(12):601-6

Contact
Jacqueline Alblas, PhD
Regenerative Medicine Center, UMC Utrecht
j.alblas@umcutrecht.nl
+31 887550294

Mailing address for correspondence
UMC Utrecht
G05.228
P.O. Box 85500
3508 GA Utrecht
The Netherlands

Mailing address for packages
idem