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ESC-Derived Perivascular Progenitor Cells: A New Treatment for Diabetes-associated Vision Loss

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Review of “Perivascular Progenitor Cells Derived From Human Embryonic Stem Cells Exhibit Functional Characteristics of Pericytes and Improve the Retinal Vasculature in a Rodent Model of Diabetic Retinopathy” from Stem Cells Translational Medicine by Stuart P. Atkinson

One of the unfortunate complications of diabetes is the weakening and rupture of blood vessels in the retina, a condition known as diabetic retinopathy (DR). One of the early events in DR is the loss of pericytes, which may aid in the formation of the brain-retinal barrier formation [1, 2], and eventually this contributes to vision loss.

While current therapies lack success, stem cell-based treatments have shown some potential [3]. This led the laboratory of Hyung-Min Chung (Konkuk University, Seoul, Republic of Korea) to assess if human embryonic stem cell-derived perivascular progenitor cells (hESC-PVPCs) could mimic pericytes and enhance vasculature repair. Their successful results, published in Stem Cells Translational Medicine, could be the first step towards the clinical investigation of stem cell-based therapy for DR and a new treatment for diabetes-associated vision loss [4].

As a first step towards their goal, the authors differentiated ESCs as embryoid bodies in the presence of BMP4 to induce mesoderm differentiation followed by a simple cell selection strategy using attachment of single cells onto collagen-coated dishes. Adherent cells expressed high levels of genes associated with blood vessel development, response to wounding, and vasculature development, and only displayed MSC- and pericyte-associated surface markers. Further pericyte-like characteristics of the cells included a spindle-like morphology, pericyte marker expression (CD140B, CD146, and NG2), multipotential differentiation (adipocytes, osteocytes, and smooth muscle cells), and appropriate perivascular localization within an in vitro vasculature.

But how do these ESC-derived perivascular progenitor cells function in vivo? The study tested the cell’s ability to improve retinal microvasculature integrity following transplant into a rat model of DR. Excitingly, following a single intravitreal injection the authors found evidence that ESC-derived perivascular progenitor cells could integrate correctly into damaged retinal blood vessels (See Figure – hESC-PVPCs labelled in Red) and significantly reduced DR-associated microvasculature leakage (See figure – PVPC vs Sham [PBS Injected])).

DR is a leading cause of blindness in working-age patients and the efficient and feasible protocol described in this study may provide us with a new and effective stem-cell based treatment. The next steps will determine whether a single injection of ESC-derived perivascular progenitor cells can retard diabetes-associated vision loss and, hopefully, confirm the therapeutic potential for pericyte and pericyte-like cells.

References

  1. Antonetti D. Eye vessels saved by rescuing their pericyte partners. Nat Med 2009;15:1248-1249.
  2. Pfister F, Przybyt E, Harmsen MC, et al. Pericytes in the eye. Pflugers Arch 2013;465:789-796.
  3. Shaw LC, Neu MB, and Grant MB. Cell-based therapies for diabetic retinopathy. Curr Diab Rep 2011;11:265-274.
  4. Kim JM, Hong KS, Song WK, et al. Perivascular Progenitor Cells Derived From Human Embryonic Stem Cells Exhibit Functional Characteristics of Pericytes and Improve the Retinal Vasculature in a Rodent Model of Diabetic Retinopathy. Stem Cells Transl Med 2016;5:1268-1276.