{"id":9036,"date":"2022-02-09T00:30:42","date_gmt":"2022-02-09T04:30:42","guid":{"rendered":"https:\/\/ambrosecelltherapy.com\/?page_id=9036"},"modified":"2023-07-13T17:22:43","modified_gmt":"2023-07-13T21:22:43","slug":"retinitis-pigmentosa-hypothesis","status":"publish","type":"page","link":"https:\/\/ambrosecelltherapy.com\/ru\/retinitis-pigmentosa-hypothesis\/","title":{"rendered":"\u0413\u0438\u043f\u043e\u0442\u0435\u0437\u0430 \u043f\u0438\u0433\u043c\u0435\u043d\u0442\u043d\u043e\u0433\u043e \u0440\u0435\u0442\u0438\u043d\u0438\u0442\u0430"},"content":{"rendered":"

[et_pb_section fb_built=”1″ admin_label=”Hero” _builder_version=”3.22.3″ background_image=”https:\/\/ambrosecelltherapy.com\/wp-content\/uploads\/2018\/12\/Cover-Revision-e1544054347204.jpg” background_blend=”multiply” custom_padding=”|||” animation_style=”zoom” animation_intensity_zoom=”4%” global_colors_info=”{}”][et_pb_row _builder_version=”3.25″ background_blend=”multiply” max_width=”80%” custom_padding=”40px|||” animation_style=”slide” animation_direction=”top” animation_intensity_slide=”3%” use_custom_width=”on” width_unit=”off” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_post_title meta=”off” featured_image=”off” text_color=”light” _builder_version=”4.14.7″ title_font=”|700||on|||||” title_font_size=”40px” text_shadow_style=”preset2″ global_colors_info=”{}”][\/et_pb_post_title][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ admin_label=”Main Body” _builder_version=”3.22.3″ custom_margin=”|||” custom_padding=”50px||30px|” global_colors_info=”{}”][et_pb_row _builder_version=”3.25″ animation_style=”fade” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”3.25″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text _builder_version=”4.14.7″ background_size=”initial” background_position=”top_left” background_repeat=”repeat” hover_enabled=”0″ global_colors_info=”{}” sticky_enabled=”0″]<\/p>\n

Summary
<\/strong>Here, we hypothesize that autologous A<\/u>dipose-D<\/u>erived R<\/u>egenerative C<\/u>ells (ADRCs) is a new option for patients living with retinitis pigmentosa. In contrast to a drug with a single mechanism of action, ADRCs regulate the multiple factors<\/em> contributing to a patient’s loss of eyesight.<\/p>\n

Background16
<\/strong>\"\"In 1857, Dr. Donders identified a group of incurable eye disorders he named retinitis pigmentosa (RP). But it was not as simple as that: Subsequently, researchers discovered over 100 genes that can contain mutations leading to retinitis pigmentosa. But genetic abnormalities do not clarify everything; half of RP cases lack previous family history and explanation.<\/p>\n

Yet, despite the disease’s complexity, able investigators have mapped out RP’s degenerative process. Retinitis means inflammation of the retina. That inflammation leads to a spiral of degeneration of the retina and optic nerve.<\/p>\n

ADRC Repair Process
<\/strong>In the presence of infection, injury, or disease, ADRCs home to sites of inflammation and initiate a repair process through multiple mechanisms of action.<\/p>\n

\"\"<\/p>\n

Time For a New Option
<\/strong>\"\"Drug and gene therapy developers continue to pursue the failed “one molecule or gene for one disease model” for RP. This minimalist approach has not produced a drug or gene therapy that changes disease progression or improves patients’ best-corrected visual acuity (BCVA).<\/p>\n

In the real world, the 100,000 people in the US diagnosed with RP lack an option that slows, stabilizes, or reverses the disease’s progression. Instead, most are legally blind by age 40. Therefore, patients need a new standard of care regardless of the gene mutation or other culprit causing RP.<\/p>\n

Hypothesis
<\/strong>Here, we hypothesize that autologous A<\/u>dipose-D<\/u>erived R<\/u>egenerative C<\/u>ells (ADRCs) is a new option for patients living with retinitis pigmentosa. In contrast to a drug with a single mechanism of action, ADRCs regulate the multiple factors<\/em> contributing to a patient’s loss of eyesight.<\/p>\n

The cornerstone of our hypothesis is that all the body’s systems are interrelated and dependent. As such, multisystem dysfunction contributes to degenerative diseases, including RP [1]<\/sup><\/a> [2]<\/sup><\/a> [3]<\/sup><\/a> [4]<\/sup><\/a> [5]<\/sup><\/a><\/p>\n

Specifically, RP-related multisystem dysregulation results in:<\/p>\n

    \n
  1. Oxidative stress,<\/li>\n
  2. Reduced nitric oxide levels,<\/li>\n
  3. Elevated systemic inflammation,<\/li>\n
  4. Abnormal immune response,<\/li>\n
  5. Metabolic dysregulation,<\/li>\n
  6. Endothelial dysfunction and<\/li>\n
  7. Mitochondrial impairment, and<\/li>\n
  8. Autonomic dysfunction.[6]<\/sup><\/a> [7]<\/sup><\/a> [8]<\/sup><\/a> [9]<\/sup><\/a><\/li>\n<\/ol>\n

    These abnormalities lead to apoptosis of the retinal photoreceptors and blindness. [10]<\/sup><\/a><\/p>\n

    \"\"<\/p>\n

    IV Protocol Rationale
    <\/strong>We propose IV delivery of ADRCs based on:<\/p>\n

      \n
    1. A rat study mimicking human RP demonstrated that IV infusion is superior to subretinal delivery. “<\/em>It would appear that stem cells exert their effect over the whole retina when administered systemically. In comparison, subretinal delivery of cells including bone marrow-derived cells usually results in rod and cone rescue”<\/em> (S. Wang 2010) [11]<\/sup><\/a><\/li>\n
    2. A human study of Umbilical Cord MSCs (UCMSCs) confirmed systemically-delivered stem cells’ feasibility, safety, and benefit. “Most patients improved their best-corrected visual acuity (BCVA) in the first three months. The proportions of patients with improved or maintained BCVA were 96.9%, 95.3%, 93.8%, 95.4%, 90.6%, and 90.6% at the 1st, 2nd, 3rd, 6th, 9th, and 12th-month follow-up, respectively. Most of the patients (81.3%) maintained or improved their visual acuities for 12 months.<\/em>” (T. Zhao 2020). The researchers also proposed that the breakdown of the blood-retinal-barrier (BRB) in the progression of RP makes it possible that infused cells can reach the impaired retinal tissue without the need for injections directly in the eye. [12]<\/sup><\/a> [13]<\/sup><\/a> [14]<\/sup><\/a><\/li>\n
    3. A study of IV injection of USMSCs vs. direct injection of a steroid showed, “UCMSC intravenous infusion shows slow but persistent action in alleviating ME (macular edema) and can improve the visual function for a longer time.”<\/em>.[15]<\/sup><\/a><\/li>\n
    4. A Japanese group compared the trophic factors secreted from fresh ADRCs vs. cultured ASCs (adipose-derived MSCs) from the same person. The study indicates that ADRCs are more multifunctional and potent than cultured ASCs cells. ADRCs released a greater variety of cytokines or soluble proteins at significantly higher amounts than ASCs. [16]<\/sup><\/a>
      The favorable comparison noted above extends to MSCs derived from other sources such as bone marrow, umbilical cord, and placenta.<\/li>\n
    5. Conversely, several direct injection studies reported adverse events such as retinal tears and fibrosis. Therefore, both the safety profile and IV infusion pathways show advantages.<\/li>\n<\/ol>\n

      AMBROSE Protocol for Retinal Diseases:<\/strong><\/p>\n

        \n
      1. A board-certified plastic surgeon, using water-assisted liposuction (WAL), harvests 400 ccs of lipoaspirate. WAL is minimally traumatic on the patient and tissue, resulting in higher ADRC yields and viability.<\/li>\n
      2. The Celution system liberates the ADRCs from the lipoaspirate.<\/li>\n
      3. A nurse inserts an IV and delivers mannitol. Mannitol is a sugar alcohol that temporarily disrupts the BRB. It is a standard of care for delivering drugs into the back of the eye.<\/li>\n
      4. The ADRCs are delivered intravenously over a 20-minute infusion.<\/li>\n<\/ol>\n

        The outpatient procedure takes about five hours. Of that time, cell preparation takes 2.5 hours, during which the patient rests comfortably.\"\"<\/p>\n

        ADRCs
        <\/strong>A<\/u>dipose-D<\/u>erived R<\/u>egenerative C<\/u>ells (ADRCs) is the designation for a clinical-grade preparation of stromal vascular fraction (SVF). ADRCs’ inherent role is maintaining cellular, tissue, and systemic homeostasis.        [17]<\/sup><\/a> [18]<\/sup><\/a> [19]<\/sup><\/a><\/p>\n

        \"\"ADRCs are a heterogeneous population of cells, including mesenchymal stem cells, other progenitor cells, fibroblasts, T-regulatory cells, and macrophages. The mix includes a high percentage of endothelial cells, endothelial progenitor cells, macrophages, and leukocytes.<\/p>\n

        \"\"After homing to an inflammatory signal, the ADRC-secretome releases hundreds of cytokines and growth factors to the diseased microenvironment. The endogenous cells send signals back to the ADRCs.<\/p>\n

        This crosstalk instructs the individual cell types necessary for repair to activate – and those not needed (or harmful) to stand down. Put differently, the plethora of biological agents in the secretome restores cellular stability and homeostasis.<\/p>\n

        \"\"<\/p>\n

        ADRCs \u2013 Miracle-Gro for Nerve Repair
        <\/strong>Miracle-Gro feeds your garden’s soil with the nutrients it needs to grow healthy roots, stems, petals, and leaves. Just as there are situations in which we fertilize a plant lacking vital nutrients, ADRCs secrete growth factors essential to the health of our aging brains, hearts, muscles, nerves, and so on.         [20]<\/a><\/sup><\/p>\n

        One such growth factor group is “Neurotrophic factors<\/strong>\u00a0(NTFs<\/strong>).” Neuro<\/em> relating to nerve and trophic<\/em>, from Ancient Greek trophik\u00f3s<\/em>, meaning\u00a0“of food or nourishment.” In other words, NTFs feed our neurons and nerves with nutrients.<\/p>\n

        Notably, Brain-Derived Neurotrophic Growth Factor (BDNF) stimulates new neurons, nerve cell connections, and nerves. It also repairs the myelin sheathing surrounding the nerves. Further, this remarkable molecule is anti-inflammatory and anti-apoptotic. Diminished BDNF levels correlate with the progression of RP. [21]<\/sup><\/a> [22]<\/sup><\/a> [23]<\/sup><\/a> [24]<\/sup><\/a> [25]<\/sup><\/a><\/p>\n

        \"\"<\/p>\n

        A recent discovery of neuroimmune cells in ADRCs is notable. Neuroimmune cells innervate tissues and release BDNF.[26]<\/sup><\/a> Additionally, other cytokines in adipose tissue secrete an abundance of neurogenerative factors.<\/p>\n

        \u00a0<\/strong>Human studies show ADRCs release factors that:<\/p>\n