Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton's Jelly Derived Mesenchymal Stem Cells
Condition: Retinitis Pigmentosa; Inherited Retinal Dystrophy
MeSH terms: Retinitis; Retinitis Pigmentosa; Retinal Dystrophies
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of this study is to determine if umbilical cord Wharton's jelly derived mesenchymal
      stem cells implanted in sub-tenon space have beneficial effects on visual functions in
      retinitis pigmentosa patients by reactivating the degenerated photoreceptors in dormant
      phase.
    

Detailed description: 
      The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier between
      photoreceptor cells and choroidal blood vessels. Photoreceptor cells are vitally and
      functionally dependent on the RPE. The conversion of blood glucose to ATP, synthesis of
      proteins in the visual cycle and removal of metabolic waste takes place in the RPE. For these
      important processes, various peptide growth factors and their receptors are synthesized in
      the RPE. More than 260 genes in the RPE are responsible for the production of these peptide
      fragments. Mutations in any of these genes as well as ischemic, physical or chemical RPE
      damage causes retinal degeneration. Retinal degeneration may be inherited, such as in
      retinitis pigmentosa (RP), Stargardt's disease, choroideremia, Best vitelliform dystrophy and
      Bietti's crystalline dystrophy. Retinal degeneration may also be acquired through genetic
      mechanisms, such as age-releated macular degeneration. In retinal degeneration, there is a
      developing loss of RPE and photoreceptors, regardless of the underlying cause.

      Umbilical cord Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) have significant
      paracrine and immunomodulatory properties. WJ-MSCs secrete trophic factors that stimulate RPE
      or secrete trophic factors that are similar to those produced by RPE. In studies using animal
      models, WJ-MSCs have been found to be effective in stopping the progression of retinal
      degeneration and for rescuing photoreceptors in the dormant phase. WJ-MSCs are
      hypoimmunogenic and have significant immunomodulatory properties. WJ-MSCs have been shown to
      suppress chronic inflammation and prevent apoptosis in animal models of neurodegenerative and
      ischemic retinal disorders. WJ-MSCs also stimulate progenitor cells in the retina and elicit
      self-repair mechanisms.

      The aim of this preliminary clinical study is to investigate the efﬁcacy of deep sub-tenon
      injected WJ-MSCs as a stem cell treatment modality for the management of retinitis
      pigmentosa, which creates outer retinal degeneration. These functional and structural effects
      were investigated using microperimetry, electrophysiology and spectral domain optical
      coherence tomography (SD-OCT). To the best of our knowledge, this is the first prospective
      clinical study that utilizes a large number of RP cases, and cases that are in phase-3.
    

Intervention name(s): Wharton's jelly derived mesenchymal stem cell
Intervention type(s): Biological
Intervention description(s): The mesenchymal cells that were used in this study were isolated from Wharton's jelly of the umbilical cord that was collected allogenicly from a single donor with the mother's consent. All cell preparation and cultivation procedures were conducted in a current Good Manufacturing Practice (cGMP) accredited laboratory (Onkim Stem Cell Technologies, Turkey).Cells were solubilized from cryopreservation before being made ready for injection. Average cell viability for each treatment was over 90.0% and each patient received cell numbers between 2-6x106 in a 1.5 ml saline solution .
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention model description: Prospective, open-label clinical trial; The statistical comparisons were made primarily between the baseline and final values from the same eye. The parametric results for visual functions and structural changes were analyzed.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Retinitis pigmentosa; Wharton's jelly derived mesenchimal stem cell; Subtenon space; Umbilical cord