• Subjects must meet the following inclusion criteria to be eligible and enroll:

• Subjects must be willing and able to provide informed consent, undergo and comply with all study assessments, and adhere to the protocol schedule.

• Patients with recurrent malignant GBM or gliosarcoma will be eligible. Patients with recurrent anaplastic astrocytoma with wild-type IDH-1 gene will also be eligible if there is a significant enhancing mass on MRI (≥1.0 cm in diameter with upper limit of 5 cm maximal diameter) because their prognosis/behavior is similar to GBM. Subjects with an initial diagnosis of an IDH-mutant grade 2 or 3 astrocytoma are also eligible at recurrence if a biopsy at recurrence is determined to be IDH-mutant grade 4 astrocytoma, and there is a significant enhancing mass on MRI (≥1.0 cm in diameter with upper limit of 5 cm maximal diameter). A pathology report constitutes adequate documentation of histology for study inclusion.

• Patients must show unequivocal evidence for tumor recurrence or progression by MRI scan after failing prior surgical resection, biopsy, chemotherapy or radiation. A baseline MRI must be performed within 24 days prior to registration. Biopsy is encouraged at the time of recurrence if it is unclear that there is recurrent tumor. However, biopsy is not required if the practicing physician thinks that there is adequate radiographic and clinical evidence for recurrence.

• Male or female patients ≥ 18 years of age.

• Patients must be able to undergo endovascular treatment based on Doppler studies showing ICA that is less than 50% occluded.

• For patients undergoing resection for biological endpoints, tumors must be surgically resectable at the time of baseline evaluation and craniotomy for tumor resection is indicated as part of their standard medical care.

• Tumors must be ≥1.0 cm in diameter with upper limit of 5 cm maximal diameter.

• Patients must have a Karnofsky performance score ≥ 70.

• Patients must have a life expectancy of at least 16 weeks.

⁃ Patients must have adequate bone marrow function (absolute granulocyte count \> 1,500 and platelet count of \> 75,000), adequate liver function (SGPT and SGOT and bilirubin \< 2 times institutional normal ranges), and adequate renal function (creatinine \< 2.0 times institutional normal) prior to starting therapy.

⁃ Prothrombin time/international normalized ratio (PT/INR) or partial thromboplastin time (PTT) ≤ 1.5x ULN.

⁃ Subjects who have received the following chemotherapies must have completed them within the following time periods prior to Baseline/Day 0 of hMSC-DNX2401 delivery with recovery from any drug-related toxic effects to Grade 1, or less, severity:

∙ Four weeks from cytotoxic agents (3 weeks from procarbazine or Temozolomide, 2 weeks from vincristine)

‣ 6 weeks from nitrosoureas (CCNU, BCNU)

‣ Four weeks from any targeted investigational agent

‣ One week from non-cytotoxic agents

⁃ This study was designed to include women and minorities, but was not designed to measure differences of intervention effects. Males and females will be recruited with no preference to gender.

⁃ No exclusion to this study will be based on race. Minorities will actively be recruited to participate. The malignant glioma patient population treated at MDACC over the past year is as follows:

∙ American Indian or Alaskan Native - 0

‣ Asian or Pacific Islander - \<2%

‣ Black, not of Hispanic Origin - 3%

‣ Hispanic - 6%

‣ White, not of Hispanic Origin - 88%

‣ Other or Unknown - 2%

‣ Total - 100%

⁃ Patients must be 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field (beyond 80% isodose line). However, if a biopsy is undertaken prior to these times and this biopsy documents histological evidence for recurrent disease, then patients will be eligible regardless of the time after radiation.

⁃ Patients must be willing to forego other cytotoxic and non-cytotoxic drug or radiation therapy against the tumor while enrolled in the study.

⁃ Women of childbearing potential must have a negative urine or serum pregnancy test at screening.

⁃ Subjects and their partners must be willing to use effective birth control during the study and for up to 6 months following administration of hMSC-DNX2401. Birth control that is acceptable to use in this study:

∙ Using twice the normal protection of birth control (i.e., double-barrier) by using a condom AND spermicidal jelly or foam, or a diaphragm AND spermicidal jelly or foam. A spermicidal jelly or foam must be used in addition to a barrier method (e.g., condom or diaphragm)

‣ Birth control pills (The Pill)

‣ Depot or injectable birth control

‣ IUD (Intrauterine Device)

‣ Birth Control Patch (e.g., Othro Evra®)

‣ NuvaRing®

‣ Surgical sterilization (i.e., tubal ligation or hysterectomy for women or vasectomy for men)