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Xeno-free Culture Reagents Improves Bone Generation by Periosteum‐derived Stem Cells

Review of “Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture” from STEM CELLS Translational Medicineby Stuart P. Atkinson

The translation of basic stem cell research into clinically relevant therapies will require xeno‐free culture components used as part of highly efficient and scalable in vitro expansion and differentiation approaches. Researchers from the laboratory of Ioannis Papantoniou (KU Leuven, Leuven, Belgium) previously established the potential of expanding and differentiating human periosteum‐derived stem cells (hPDCs), crucial to bone fracture healing in vivo [1], in microcarrier‐containing bioreactors [2] as a means to develop sources of cells with osteogenic or chondrogenic potential for in vivo transplantation. 

The authors return with a new STEM CELLS Translational Medicine article that now factors in the replacement of fetal bovine serum (FBS) with human platelet lysate (HPL),  a xeno-free product containing a wide range of growth factors and adhesive proteins [3, 4]. Encouragingly, Gupta et al. report that replacing FBS with HPL increases the expansion efficiency and bone-forming capacity of hPDCs grown in microcarrier‐containing bioreactor culture [5].

Can this culture strategy take stem cell-mediated bone repair a step further towards treating human patients?

The authors first discovered that hPDCs cultured on macroporous gelatin-coated microcarrier beads in scalable and flexible spinner flask cultures displayed a faster proliferation rate in the presence of HPL when compared to FBS. Of note, an increased proliferation rate may result in a reduction in the overall culture time required and, therefore, an increase in cost efficiency. HPL-cultured hPDCs also maintained cell viability, MSC-like phenotypic marker expression, and trilineage differentiation capability, although the study noted a slight reduction in adipogenic potential, perhaps due to the altered transcriptional profiles observed for the hPDC populations under comparison. Alterations included increased expression of the SOX9 master regulator of chondrogenesis, the RUNX2 osteochondroprogenitor cell marker, and the BMP2 and WNT5A MSC osteogenic differentiation factors in HPL-cultured hPDCs.

Following ectopic implantation in an immunodeficient mouse model within calcium phosphate scaffolds, HPL-cultured hPDCs generated significant levels of mineralized tissue, when compared to the fibrous tissue generated by FBS-cultured hPDCs, thanks to an increase in the osteogenic capacity of hPSCs brought upon by WNT and BMP pathway activation. Excitingly, further analysis by the authors suggested that HPL-cultured hPSCs generated newly formed bone associated with new blood vessels.

Overall, this fascinating new study highlights the potential of HPL as a replacement for FBS, hPDCs in bone regeneration, microcarrier spinner flask culture in stem cell expansion, and their combination as a potentially effective means to take hPDC-mediated bone repair to the clinic. To advance this research line, the authors now hope to study the osteogenic capacity of hPDCs in response to different batches of HPL and explore the serial expansion of hPDCs freshly isolated from periost biopsies in the attainment of clinically relevant numbers of cells.

For more on hPDCs, effective xeno-free culture components, and repairing/regenerating bone, stay tuned to the Stem Cells Portal!

References

  1. Duchamp de Lageneste O, Julien A, Abou-Khalil R, et al., Periosteum contains skeletal stem cells with high bone regenerative potential controlled by Periostin. Nature Communications 2018;9:773.
  2. Sonnaert M, Papantoniou I, Bloemen V, et al., Human periosteal-derived cell expansion in a perfusion bioreactor system: proliferation, differentiation and extracellular matrix formation. Journal of Tissue Engineering and Regenerative Medicine 2017;11:519-530.
  3. Müller AM, Davenport M, Verrier S, et al., Platelet Lysate as a Serum Substitute for 2D Static and 3D Perfusion Culture of Stromal Vascular Fraction Cells from Human Adipose Tissue. Tissue Engineering Part A 2009;15:869-875.
  4. Doucet C, Ernou I, Zhang Y, et al., Platelet lysates promote mesenchymal stem cell expansion: A safety substitute for animal serum in cell-based therapy applications. Journal of Cellular Physiology 2005;205:228-236.
  5. Gupta P, Hall GN, Geris L, et al., Human Platelet Lysate Improves Bone Forming Potential of Human Progenitor Cells Expanded in Microcarrier-Based Dynamic Culture. STEM CELLS Translational Medicine 2019;8:810-821.