BACKGROUND　Type　1　diabetes　(T1D)　results　from　the　autoimmune-mediated　loss　of　pancreatic　beta-cells.　Current　insulin　therapies　offer　symptomatic　relief　but　fall　short　of　providing　a　definitive　cure.　Islet　cell　transplantation,　while　promising,　faces　limitations　related　to　donor　scarcity,　procedural　complexities,　and　the　necessity　for　long-term　immunosuppression.　Consequently,　there　is　an　urgent　need　for　innovative　strategies　aimed　at　beta-cell　regeneration.　Patient-derived　induced　pluripotent　stem　cells　(iPSCs),　obtained　from　peripheral　blood　mononuclear　cells　(PBMCs)　of　T1D　patients,　hold　great　potential　as　a　source　of　cells　for　therapeutic　purposes.　Therefore,　the　differentiation　of　T1D-iPSCs　into　functional　pancreatic　beta-cells　is　a　critical　step　toward　effective　beta-cell　replacement　therapy.　AIM　To　assess　the　potential　of　patient-derived　T1D-beta-like　cells　(differentiated　from　T1D-iPSCs　reprogrammed　from　T1D-PBMCs)　for　restoring　beta-cell　function　in　T1D.　METHODS　T1D-iPSCs　were　reprogrammed　from　T1D-PBMCs　using　an　episomal　vector-based　approach.　Pluripotency　was　confirmed　by　flow　cytometry　(FCM),　quantitative　real-time　polymerase　chain　reaction,　genomic　stability　analysis,　and　teratoma　formation　assays.　Differentiation　into　pancreatic　beta-cells　was　optimized　using　triiodothyronine　(T3),　vitamin　C　(Vc),　and　an　adenovirus　(M3C)　encoding　pancreatic　duodenal　homeobox-1,　neurogenin　3　(Ngn3),　and　MAF　bZIP　transcription　factor　A　(MafA).　Following　characterization　of　beta-cell　features　by　immunofluorescence,　quantitative　real-time　polymerase　chain　reaction,　and　flow　cytometry,　therapeutic　efficacy　was　assessed　through　blood　glucose　monitoring　after　transplantation　under　the　renal　capsule　of　streptozotocin-induced　diabetic　mice.　RESULTS　T1D-iPSCs　were　successfully　generated　from　T1D-PBMCs.　These　cells　exhibited　the　hallmark　characteristics　of　pluripotent　stem　cells,　including　appropriate　morphology,　differentiation　potential,　genomic　integrity,　and　expression　of　pluripotency-associated　genes.　Differentiation　yielded　insulin-positive　(insulin+)　pancreatic　beta-like　cells　that,　at　the　mRNA　level,　expressed　key　beta-cell　markers　such　as　pancreatic　duodenal　homeobox-1,　Ngn3,　MafA,　NeuroD,　glucagon-like　peptide-1　receptor,　Nkx6.1,　glucose　transporter　2,　and　Kir6.2.　Notably,　the　T3　+　Vc　group　displayed　the　lowest　Ngn3　expression　(1.31　+/-　0.38　vs　1.96　+/-　0.25　vs　2.51　+/-　0.24,　P　＜　0.01),　while　the　M3C　+　T3　+　Vc　group　exhibited　the　highest　MafA　expression　(0.49　+/-　0.11　vs　0.32　+/-　0.06　vs　0.29　+/-　0.08,　P　＜　0.05).　Both　in　vitro　and　in　vivo　assessments　confirmed　the　insulin　secretion　ability　of　the　generated　beta-like　cells;　however,　they　did　not　demonstrate　appropriate　modulation　of　insulin　release　in　response　to　variations　in　extracellular　glucose　concentrations.　CONCLUSION　T1D-iPSCs　derived　from　T1D-PBMCs　can　be　differentiated　into　insulin+　beta-like　cells,　albeit　with　functional　immaturity.　These　cells　represent　a　potential　source　of　seed　cells　for　beta-cell　replacement　therapy　in　T1D.